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CD133 is one of the most representative cancer stem cell markers. This study evaluated the potential prognostic value of CD133 expression in stage I lung adenocarcinomas (ADC). Tumors from 177 patients were immunohistochemically examined for CD133 expression, and their associations with disease recurrence were analyzed. Also, the potential prognostic value of combining CD133 expression with proliferating activity measured by immunohistochemical expression of Ki-67 and vessel involvement was evaluated. CD133 high expressers showed a significantly higher risk of recurrence than CD133 low expressers: 5-year disease-free survival (DFS) rate 77.2% vs. 95.1% (p=0.004), adjusted Hazard ratio (HR) 4.37, 95% Confidence Interval (CI) 1.30-14.71 (p=0.017). CD133 high expressers having strong proliferating activity and/or with vessel invasion showed a higher risk of recurrence: 5-year DFS rate 66.5% in CD133 high/Ki-67 high expressers vs. 93.2% in the other types (p<0.001), adjusted HR 8.39, 95% CI 2.65-26.54 (p<0.001): 5-year DFS rate 51.0% in CD133 high expressers with vessel invasion vs. 92.9% in the other types (p<0.001), adjusted HR 4.50, 95% CI 1.51-13.34 (p=0.007): 5-year DFS rate 53.9% in CD133 high/Ki-67 high expressers with vessel invasion vs. 91.2% in the other types (p<0.001), adjusted HR 9.32, 95% CI 3.42-25.39 (p<0.001). In conclusion, the level of CD133 expression is an independent prognostic marker and its combination with proliferating activity and/or vessel invasion could have excellent prognostic value to predict postoperative recurrence in patients with stage I lung ADC.

Although CD133 has been shown to be a marker for cancer stem cells in various tumours, its expression in pancreatic cancer has not yet been clinically reported. In this study, we investigated the relationship between CD133 expression and clinicopathological factors in pancreatic cancer. Pancreatic head carcinoma specimens from 80 patients who underwent surgical resection were immunohistochemically assessed for CD133, vascular endothelial growth factor (VEGF)-C, CXCR4, CD34, Ki-67, and cytokeratin (CK) expressions. Sixty percentage (48/80) of specimens were CD133-positive, with less than 15% cells per specimen expressing the marker. CD133-positive cells were found at the peripheral site of adenocarcinoma glandular structures and were negative for CK. There was a significant correlation between CD133 expression and clinicopathological factors, including histological type, lymphatic invasion, and lymph node metastasis (P=0.0215, 0.0023, and 0.0024, respectively). Vascular endothelial growth factor-C expression was also significantly correlated with CD133 expression (P=0.0002). Consequently, the 5-year survival rate of CD133-positive patients was significantly lower than that of CD133-negative patients (P=0.0002) and multivariate analysis revealed that CD133 expression was an independent prognostic factor (P=0.0103). These results suggest that CD133 expression in pancreatic cancer was significantly associated with lymphatic metastasis, VEGF-C expression, and prognosis.

Background

To investigate on expressions and clinical significances of CD133 protein and vasculogenic mimicry (VM) in primary non-small cell lung cancer (NSCLC).

Methods

The specimens of NSCLC from 305 Chinese patients with follow-up were analyzed for CD133 protein expression and VM by immunohistochemical and histochemical staining.

Results

In NSCLC, positive rates of 48.9% and 35.7% were obtained for CD133 and VM, respectively. The VM and expression of CD133 were significantly higher in carcinoma than in normal. There were a positive relationship between the VM and expression of CD133 and the tumor grade, lymph node metastasis and clinical stage (all P<0.05). The overall mean survival time of the patients with CD133 and VM positive expression was lower than that of patients with negative expression. Microvessel density (MVD) was positive corresponded with the grade, lymph node metastasis and clinical stage (all P<0.05). The overall mean survival time of the patients with MVD≥22’s group was shorter than that of patients with MVD<22’s group. Pathological-tumor-node-metastasis (pTNM) stage, positive expression of CD133 and VM, postoperative therapy and MVD were independent prognostic factors of NSCLC (P<0.05). Immunohistochemistry revealed an important intratumoral heterogeneity in all four CD133 expression profiles.

Conclusions

VM, MVD and expression of CD133 are related to differentiation, lymph node metastasis, clinical stage, and prognosis. It is suggested that CD133, VM and MVD should be considered as a potential marker for the prognosis.

Background

To study on expressions and clinical significances of CD133 protein and CD133 mRNA in primary lesion of gastric adenocarcinoma (GC).

Methods

Expressions of CD133 protein by immunostaining (99 cases) and CD133 mRNA by semi-quantitative RT-PCR (31 cases) were detected in primary lesion and in noncancerous gastric mucosa tissue (NCGT). Correlations of CD133 protein expression with clinicopathological parameters and post-operative survival were analyzed. Relations of CD133 mRNA level with Ki-67 labeling index (LI), and lymphatic metastasis were assessed too.

Results

Brown particles indicating CD133 protein positivity occurred in some parts of tumor cells and epithelium. Expressive percentage of CD133 protein positivity was significantly higher in subgroups with >5 cm diameter (P = 0.041), later TNM stage (P = 0.044), severer lymph node metastasis (P = 0.017), occurrences of lymphatic invasion (P = 0.000) and vascular invasion (P = 0.000) respectively. Severer invasion depth (P = 0.011), lymph node metastasis occurrence (P = 0.043) and later TNM stage (P = 0.049) were the independent risk factors for CD133 protein expression. Average brightness scale value (BSV) of CD133 mRNA was significantly higher in subgroups with >5 cm diameter (P = 0.041), lymph node metastasis occurrence (P = 0.004) and in lower Ki-67 LI (P = 0.02). Relative analysis revealed that BSV of CD133 mRNA related positively to metastatic lymphatic nodes ratio (P = 0.008) and metastatic lymph node number (P = 0.009), but negatively to Ki-67 LI (P = 0.009). Survival of positive subgroup of CD 133 protein was significantly poorer (P = 0.047). Lymph node metastasis occurrence (P = 0.042), later TNM stage (P = 0.046) and CD 133 protein positive expression (P = 0.046) were respectively the independent risk factors to survival.

Conclusion

Higher expressive level of CD133 mRNA is associated to lower Ki-67 LI and severer lymphatic metastasis. Therefore, the expressive level of CD133 mRNA can play an appropriate role to reflect the status of lymph node metastasis and proliferation of GC. CD133 protein expression is closely related with larger tumor, later TNM stage, lymphtic metastasis and survival of GC.

AIM: To investigate the expression of leukemia related protein 16 (LRP16), and the possible relationship between LRP16 expression and clinicopathological indices in 336 gastric carcinoma patients.

METHODS: Immunohistochemistry was used to detect LRP16 expression in 336 cases of paraffin-embedded gastric carcinoma tissues and 60 cases of distal normal mucosa. The relationships between LRP16 expression and patients’ age, tumor size, histological grade, clinical stage, metastatic status and prognosis were analysed.

RESULTS: The expression of LRP16 was 58.6% (197/336) in gastric carcinoma and 31.7% (19/60) in distal normal gastric mucosa. The expression of LRP16 in carcinoma was significantly higher than that in normal mucosa tissues (χ2 = 14.929, P = 0.001). LRP16 protein expression was found in 44.1% (63/143) carcinomas at stage I and II, and 69.4% (134/193) carcinomas at stage III and IV (χ2 = 21.804, P = 0.001), and in 56.9% (182/320) of cancers without metastasis but 93.8% (15/16) of those with metastasis (χ2 = 8.543, P = 0.003). The expression of LRP16 was correlated with tumor size, infiltrative depth, clinical stage, lymphatic invasion and distant metastasis (all P < 0.05). Follow-up data showed that there was a significant difference in median survival time between cancer patients with expression of LRP16 (27.0 mo) and those without (48.0 mo, Log rank =31.644, P = 0.001).

CONCLUSION: The expression of LRP16 may be associated with invasion, metastasis and prognosis of gastric cancer.

AIM: To analyze the differences and relevance of Yes-associated protein (YAP) and survivin, and to explore the correlation and significance of their expression in gastric carcinoma and precancerous lesions.

METHODS: The PV9000 immunohistochemical method was used to detect the expression of YAP and survivin in 98 cases of normal gastric mucosa, 58 intestinal metaplasia (IM), 32 dysplasia and 98 gastric carcinoma.

RESULTS: The positive rates of YAP in dysplasia (37.5%) and gastric carcinoma (48.0%) were significantly higher than that in normal gastric mucosa (13.3%), P < 0.01. The positive rates of survivin in IM (53.4%), dysplasia (59.4%) and gastric carcinoma (65.3%) were significantly higher than in normal gastric mucosa (11.2%), P < 0.01. Survivin expression gradually increased from 41.7% in well differentiated adenocarcinoma through 58.3% in moderately differentiated adenocarcinoma to 75.6% in poorly differentiated adenocarcinoma, with significant Rank correlation, rk = 0.279, P < 0.01. The positive rate of survivin in gastric carcinoma of diffused type (74.6%) was significantly higher than that in intestinal type (51.3%), P < 0.05. In gastric carcinoma with lymph node metastasis (76.9%), the positive rate of survivin was significantly higher than that in the group without lymph node metastasis (41.2%), P < 0.01. In 98 cases of gastric carcinoma, the expression of YAP and of survivin were positively correlated, rk = 0.246, P < 0.01.

CONCLUSION: YAP may play an important role as a carcinogenic factor and may induce survivin expression. Detecting both markers together may help in early diagnosis of gastric carcinoma.

We performed immunohistochemical staining against Hepatocyte (Hep) and CD10 antibodies in 75 hepatocellular carcinoma (HCC), 50 cholangiocarcinomas, 49 colorectal adenocarcinomas, and 308 gastric adenocarcinomas by tissue array method. We also evaluated the various non-neoplastic adult tissues and fetal digestive organs. Hep was expressed in 80% of HCCs, and HCCs without Hep expression were more likely to have a higher Edmondson & Steiner grade than HCCs with Hep expression (p=0.004). In non-HCCs, 16% of cholangiocarcinomas, 8.2% of colorectal carcinomas, and 44.2% of gastric carcinomas expressed Hep. Gastric carcinomas with Hep expression were significantly associated with early gastric carcinomas (p<0.001). In non-neoplastic tissues, Hep was found expressed in normal hepatocytes, small intestinal mucosa, and intestinal metaplasia of the stomach. Fetal hepatocytes expressed Hep after 19 weeks of gestation. CD10 was detected in 46.7% (35/75) of HCCs, and canalicular staining pattern was predominant in HCCs. In conclusion, the expression of Hep and CD10 may help to distinguish HCCs from non-HCCs.

Loss of the coxsackie and adenovirus receptor (CAR) has previously been observed in gastric cancer. The role of CAR in gastric cancer pathobiology, however, is unclear. We therefore analysed CAR in 196 R0-resected gastric adenocarcinomas and non-cancerous gastric mucosa samples using immunohistochemistry and immunofluorescence. Coxsackie and adenovirus receptor was found at the surface and foveolar epithelium of all non-neoplastic gastric mucosa samples (n=175), whereas only 56% of gastric cancer specimens showed CAR positivity (P<0.0001). Loss of CAR correlated significantly with decreased differentiation, increased infiltrative depths, presence of distant metastases, and was also associated with reduced carcinoma-specific survival. To clarify whether CAR impacts the tumorbiologic properties of gastric cancer, we subsequently determined the role of CAR in proliferation, migration, and invasion of gastric cancer cell lines by application of specific CAR siRNA or ectopic expression of a human full-length CAR cDNA. These experiments showed that RNAi-mediated CAR knock down resulted in increased proliferation, migration, and invasion of gastric cancer cell lines, whereas enforced ectopic CAR expression led to opposite effects. We conclude that the association of reduced presence of CAR in more severe disease states, together with our findings in gastric cancer cell lines, suggests that CAR functionally contributes to gastric cancer pathogenesis, showing features of a tumour suppressor.

AIM: To analyze the serum levels and prognostic significance of vascular endothelial growth factor (VEGF) -A, -C, and -D, and their receptors, VEGFR-1 and -2 in gastric adenocarcinomas.

METHODS: The serum levels of VEGF family members were measured in 76 control subjects and 76 patients with gastric adenocarcinoma using an enzyme-linked immunosorbent assay (ELISA). These measurements were correlated with clinco-pathological features and survival rates.

RESULTS: The serum levels of VEGF-A and its receptor, VEGFR-1, were significantly higher in patients with gastric cancer than in healthy donors (t = 2.3, P = 0.02 and t = 4.2, P < 0.0001, respectively). In contrast, the serum levels of VEGF-D were significantly higher in control subjects than in patients (t = 2.9, P = 0.004). There was no significant difference in serum levels of VEGF-C and VEGFR-2 between patients and controls. VEGF-C was associated with advanced tumor stage and presence of metastasis. VEGFR-1 was associated with metastasis, advanced overall stage, tumor differentiation and survival. VEGFR-2 levels were associated with poor tumor differentiation. There was no significant prognostic value for any of the VEGF family members or their receptors except for VEGFR-1 where high levels were associated with a poor overall survival.

CONCLUSION: Serum VEGF levels vary significantly in the same cohort of patients with variable clinico-pathological features and prognostic values. The simultaneous measurement of VEGF receptors levels in sera may overcome the limitations of a single biomarker assay.

We have studied the expression of p53 in 206 patients with gastric adenocarcinomas. A standard immunohistochemical technique employing the CM-1 anti-p53 polyclonal antibody was applied to the routinely fixed and paraffin-embedded material from these tumours; overexpression of p53 was defined as positive nuclear staining: 46% (94/206) of gastric carcinomas expressed high levels of p53. There was no significant correlation between p53 positivity and the tumour grade, growth pattern, the Lauren type or lymph node metastases. Correlation with disease stage was only marginally significant (P = 0.05). Life table analysis revealed a highly significant association between p53 expression and survival (P = 0.0062), the odds ratio of death being 1.89 (95% confidence interval 1.33-2.69). The overall 5-year survival of patients with p53-positive tumours was 3% compared with 16% for those with p53-negative tumours (median survival time being 5.6 and 11.4 months respectively). These data suggest that overexpression of the p53 oncoprotein is an independent marker of shortened survival in gastric cancer patients.

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The study investigated hypoxia-associated markers (HIF-2α, Epo, Epo-R, Glut-1 and VEGF) along with Ki-67 in a gastric carcinogenesis model, and the prognostic significance of hypoxia-inducible factor (HIF)-2α in surgically treated gastro-oesophageal cancer. Protein expression was examined using immunohistochemistry on formalin-fixed, paraffin-embedded biopsies of normal mucosa (n=20), Helicobacter pylori-associated gastritis (n=24), intestinal metaplasia (n=24), dysplasia (n=12) and intestinal (n=19) and diffuse (n=21) adenocarcinoma. Relationships between HIF-2α expression and prognosis were assessed in resection specimens from 177 patients with gastric and gastro-oesophageal junction adenocarcinoma. Expression of all markers increased with progression along the gastric carcinogenesis sequence (P=0.0001). Hypoxia-inducible factor-2α was expressed in 63% of 177 resection specimens and at a high level in 44%. The median overall survival in patients with HIF-2α-expressing tumours was 22 (95% CI 18−26) months, whereas those with HIF-2α-negative tumours had a median survival of 37 (95% CI 29−44) months (P=0.015). Hypoxia-inducible factor-2α had no independent prognostic significance in multivariate analysis. In view of the lack of independent prognostic significance, HIF-2α has no role as a routine prognostic indicator. However, the high expression of HIF-2α suggests that it may be of value as a potential therapeutic target.

RASSF2 has recently been identified as a potential tumor suppressor that serves as a Ras effector in various types of human cancers. However, there have been few reports detailing this in gastric cancer. Samples of gastric adenocarcinoma from 276 Chinese patients with follow-up were analyzed for RASSF2 protein expression by immunohistochemistry. RASSF2 was expressed in up to 31.2% (86/276) of this group of gastric carcinoma. The expression of RASSF2 was significantly lower in carcinomas than in normal mucosas (P<0.05). RASSF2 corresponded positively with patient age, histological differentiation, depth of tumor invasion, regional lymph node and distant metastasis, and TNM stage (all P<0.05). Further multivariate analysis revealed that patient gender, depth of tumor invasion, distant metastasis, TNM stage and the expression of RASSF2 were independent prognostic factors for patients with gastric cancer. The Kaplan-Meier plot showed that the overall mean survival time of the patients with RASSF2-negative expression was shorter than that of patients with positive expression (χ2=156.874, P<0.0001). Moreover, RASSF2-negative expression had a much more significant effect on the survival of those patients with early stage tumors (χ2=127.167, P<0.0001), highlighted by a >50.9% reduction in 3-year survival compared to that of patients with RASSF2-positive expression. In late stages, the difference was also significant (χ2=6.246, P=0.019), with a 35.5% reduction in 3-year survival. It is suggested that RASSF2 plays an important role in the evolution of gastric adenocarcinoma and should be considered as a potential marker for its prognosis.

Background: To evaluate the prognostic implication of cancer stem cell markers in pancreac ductal adenocarcinoma (PDAC), the expression of CD133 and nestin were investigated in a series of PDAC patients in relation to the survival rate. Methods: This series included 42 cases of PDAC patients and evaluated the stem cell markers CD133 and nestin expression detected by immunohistochemistry. The presence of immunopositive tumor cells considering intensity and area was evaluated and interpreted in comparison to the patients’ clinicopathological and survival data. Results: Twenty eight cases (66.7%) showed high CD133 expression. The CD133 expression was mainly identified in the apical border of the tumor cell, but aberrant expression in the cytoplasmic or perinuclear location was also noted. High nestin expression in tumor cells were found in only 2 cases, but high nestin expression along perinuerial or stromal region was found in 15 cases (35.7%). There was no correlation between CD133, nestin expression and gemcitabine resistance. Statistically significant difference was found in patient survival in N stage (p=0.007), and CD133 expression (p= 0.014) in univariate analysis. Nestin expression wan not statistically significant, but it was helpful to identify the perineurial invasion. In Cox-regression hazard model stratified by age and sex for multivariable analysis, AJCC stage and CD133 were independent prognostic factors for overall survival. Conclusions: CD133 expression is upregulated in PDAC that is related to poor prognosis, and treatment targeted the CD133 positive cancer/cancer stem cells might be a promising therapeutic strategy for this patients.

Background

This study was designed to investigate EGFR protein expression, EGFR copy number and EGFR mutations in lung adenocarcinomas, to explore the relationship of the three markers.

Methods

EGFR status was analyzed in surgically resected lung adenocarcinoma samples from 133 Chinese patients by three methods: protein expression (n = 133) by standardized immunohistochemistry (IHC), gene copy number (n = 133) by fluorescence in situ hybridization (FISH), and mutation analysis using the Scorpion amplification refractory mutation system (ARMS) (n = 133).

Results

The results showed that 68.4% of the samples were positive by IHC, 42.1% were positive by FISH, and 63.9% contained activating kinase domain mutations. EGFR mutations were more frequent in non-smoking patients (p = 0.008), and EGFR mutations were associated with EGFR FISH positivity (p < 0.0001). When using 10% positivity and 2+ as cutoffs, EGFR protein expression was significantly correlated with EGFR FISH positivity (p = 0.012) and EGFR mutations (p = 0.008) after Bonferroni correction.

Conclusion

EGFR protein expression, EGFR copy number and EGFR mutations were closely related to each other. Standard methods and interpretation criteria need to be established.

Background

CD133 was recently reported to be a cancer stem cell marker and a prognostic marker for several tumors. However, few studies have investigated CD133 expression in esophageal squamous cell carcinoma (ESCC). Therefore, we examined whether CD133 could serve as a prognostic marker of ESCC and investigated the correlation between CD133 expression and the clinicopathological findings of ESCC patients and several markers.

Methods

We studied 86 ESCC patients who underwent curative surgery without neoadjuvant treatment at Tohoku University Hospital (Sendai, Japan) between January 2000 and December 2005. We analyzed tissue specimens by immunohistochemical staining for CD133, p53, p16, p27, murine double minute 2 (MDM2), Ki-67, and epidermal growth factor receptor (EGFR).

Results

Pathological tumor depth and tumor stage were significantly more advanced among CD133-negative patients than among CD133-positive patients. A log-rank test showed that CD133 immunoreactivity was significantly correlated with the overall survival of the patients (P = 0.049). However, multivariate analysis showed that it was not significantly correlated (P = 0.078). Moreover, CD133 was significantly positively correlated with p27 immunoreactivity (P = 0.0013) and tended to be positively correlated with p16 immunoreactivity (P = 0.057). In addition, p16 immunoreactivity was correlated with smoking history (P = 0.018), pathological lymph node status (P = 0.033), and lymphatic invasion (P = 0.018).

Conclusions

This study indicated that CD133 immunoreactivity is a good predictor of prognosis in ESCC patients. In addition, CD133 may play a role in the regulation of tumor cell cycle through p27 and p16 in ESCC. At present, it thus remains controversial whether CD133 expression is a valid prognostic marker for ESCC. To elucidate this relationship, further investigations are required.

Background:

Gastric carcinogenesis has been well documented in the step-wise histopathological model, known as Correa pathway. Several biomarkers including CD44, Musashi-1 and CD133 have been reported as putative stem cell (PSC) markers.

Methods:

We investigated expression of PSC markers CD44, Musashi-1 and CD133 in relation to gastric carcinogenesis and prognosis and chemoresponse. Immunohistochemistry staining was performed in gastric cancer (GC) clinical specimens representing different steps of the Correa pathway. Gastric cancer samples taken before and after neoadjuvant chemotherapy with docetaxel, cisplatin and capecitabine (DCX) were also evaluated for PSC marker expression.

Results:

We showed that the expression of three PSC markers was significantly elevated in GC relative to normal gastric mucosa (P<0.001 for each marker). Precancerous lesions, including intestinal metaplasia and dysplasia, demonstrated increased expression of CD44 and Musashi-1. CD133 was predominantly expressed along the border between intramucosal carcinoma and connective tissue at later stages. High CD44 and CD133 expression showed prognostic value for worse patient survival (P=0.014 and P=0.019, respectively). A small number of tumours with high expression of CD44 and CD133 showed pathological response to DCX-based neoadjuvant chemotherapy.

Conclusion:

CD44 and Musashi-1 are frequently expressed in both premalignant gastric lesions and invasive GC, whereas CD133 expression is restricted mainly to neoplastic tissues.

In this study, we characterized the intratumoral expression of IL-17 and CD8+ TILs in gastric adenocarcinoma patients after resection and determined the correlation between the survival probability of gastric adenocarcinoma patients and the expression of IL-17 in tumor. Expression of IL-17 and CD8 was assessed by immunohistochemistry, and the prognostic effects of intratumoral IL-17 expression and CD8+ TILs were evaluated by Cox regression and Kaplan-Meier analysis. Immunohistochemical detection revealed the presence of IL-17 and CD8+ cells in gastric adenocarcinoma tissue samples (90.6%, 174 out of 192 patients and 96.9%, 186 out of 192 patients, respectively). We have also found that intratumoral IL-17 expression was significantly correlated with age (p=0.004) and that the number of CD8+ TILs was significantly correlated with UICC staging (p=0.012) and the depth of tumor invasion (p=0.022). The five-year overall survival probability among patients intratumorally expressing higher levels of IL-17 was significantly better than those expressing lower levels of IL-17 (p=0.036). Multivariate Cox proportional hazard analyses revealed that intratumoral IL-17 expression (HR: 0.521; 95% CI: 0.329-0.823; p=0.005) was an independent factor affecting the five-year overall survival probability. We conclude that low levels of intratumoral IL-17 expression may indicate poor prognosis in gastric adenocarcinoma patients.

Sialyl Lewis xantigen (SLX) is a carbohydrate antigen that serves as a ligand for selectin, an adhesion molecule expressed on vascular endothelial cells. The expression of SLX in 245 patients with advanced gastric carcinoma was examined immunohistochemically, and its clinicopathologic significance was analysed. We classified the patients with advanced gastric carcinoma into 91 with differentiated type and 154 with undifferentiated type. SLX expressed in 135 of 245 patients (55%), comprising 68 (75%) patients with differentiated carcinoma and 67 (44%) with undifferentiated carcinoma. The positive rate for SLX expression was significantly higher among patients with differentiated carcinoma than among those in undifferentiated carcinoma (P < 0.0001). With differentiated carcinoma, the incidence of lymph node metastasis, advanced tumour stage (stage III and IV) and liver recurrence was significantly higher in SLX-positive patients than in SLX-negative ones (P  < .0001, P = 0.0065 and P = 0.028, respectively). Moreover, the prognoses were better in patients with SLX-negative tumours than in those with SLX-positive tumours (P = 0.019). With undifferentiated carcinoma, there were no significant correlations between SLX expression and any clinicopathological features or prognoses. The clinicopathologic significance of SLX expression in gastric carcinoma patients depends on histologic type. SLX expression may be of great relevance in predicting liver metastases in patients with differentiated carcinoma. © 2000 Cancer Research Campaign http://www.bjcancer.com

Sinonasal inverted papilloma (IP) is a primary benign lesion with a tendency for local recurrence. Malignant transformation may develop in up to 15% of cases. Fascin (Fascin 1) is an actin cross-link binding protein required for the formation of actin-based cell-surface protrusions and cell motility. Fascin up-regulation in lung, gastric, breast and hepatobiliary carcinomas correlates with aggressiveness and decreased survival. Here we evaluate immunohistochemical expression of fascin in 47 sinonasal IPs from 34 patients. Fascin over-expression is significantly more common in sinonasal IP with high-grade dysplasia than in those with no dysplastic or low-grade dysplastic epithelium (P = 0.0001). No significant change in fascin expression is seen with recurrence. Over expression of fascin in high-grade dysplastic epithelium in IP may be associated with tumor progression and malignant transformation.

AIM: To investigate the expression of Popeye domain containing 3 (Popdc3) and its correlation with clinicopathological features and prognosis of gastric cancer.

METHODS: The method of immunohistochemistry was used to investigate the expression of Popdc3 in 306 cases of human gastric cancer and 84 noncancerous gastric tissues. Simultaneously, the relationship between Popdc3 expression and the survival of the patients was retrospectively analyzed.

RESULTS: Popdc3 was detected in 72 (85.71%) of 84 human nontumor mucosa. High expression of Popdc3 protein was detected in 78 (25.49%) of 306 human gastric cancer cases, and low expression was detected in 228 (74.51%). Low expression of Popdc3 correlated with depth of invasion (P < 0.0001), regional lymph nodes (P < 0.0001) and distant metastasis (P = 0.02), and tumor, nodes, metastasis (TNM) stages (P < 0.0001). On multivariate analysis, only the patient’s gender, regional lymph node metastasis, distant metastasis, TNM stages, and the expression of Popdc3 were independent prognostic factors in patients with gastric cancer. The Kaplan-Meier plot showed that low Popdc3 expression had a much more significant effect on the survival of those patients with early-stage tumors (χ2 = 104.741, P < 0.0001), with a > 51.9% reduction in the three-year survival compared with high Popdc3 expression. In late stages, the difference was also significant (χ2 = 5.930, P = 0.015), with a 32.6% reduction in the three-year survival.

CONCLUSION: Reduced expression of Popdc3 may play a significant role in the carcinogenesis and progression of gastric cancer. Popdc3 may be an independent prognostic factor.

Objective

The aim of this study was to detect metastasis-associated in colon cancer-1 (MACC1) expression in Chinese gastric cancer and analyze the relationship between MACC1 expression and postoperative survival.

Methods

The expression of MACC1 and c-MET protein in a sample of 128 gastric cancer tissues was detected by immunohistochemistry. A retrospective cohort study on the prognosis was carried out and data were collected from medical records.

Results

The positive rate of MACC1 protein expression in gastric cancer was 47.66%, higher than that in adjacent noncancerous mucosa (P<0.001). MACC1 protein expression was not related to the clinicopathological variables involved. Kaplan-Meier analysis revealed that the survival of MACC1 positive group tended to be better than that of MACC1 negative group, particularly in patients with stage III carcinoma (P=0.032). Cox regression analysis revealed that MACC1 protein over-expression in gastric cancer tended to be a protective factor with hazard ratio of 0.621 (P=0.057). Immunohistochemical analysis showed that the positive rate of c-MET protein expression was much higher in cases with positive MACC1 expression in gastric cancer (P=0.002), but P53 expression was not associated with MACC1 expression.

Conclusion

MACC1 over-expression implies better survival and may be an independent prognostic factor for gastric cancer in Chinese patients.

The cancer stem cell (CSC) model suggests that high levels of CSCs within a tumor are associated with poor prognosis. The aim of this study was to investigate the expression of the stem cell marker CD133 in clear cell renal cell carcinoma (ccRCC), and its prognostic significance. The expression of CD133 was examined in 140 cases of ccRCC using immunohistochemistry. Ki-67 and Oct-4 were double-immunostained with CD133 to evaluate the proliferative activity and the stemness of CD133-expressing cells, respectively. CD133 expression was observed in 45 cases (32.1%) and high levels of expression were found to be associated with a macro-/microcystic pattern, non-sarcomatoid changes and non-metastatic disease. The Ki-67 labeling index tended to be lower in CD133-expressing ccRCCs compared to non-expressing tumors. CD133-expressing tumor cells rarely expressed Oct-4. A high degree of CD133 expression was observed in ccRCC with more differentiated morphology and non-metastatic disease, suggesting that CD133 is a favorable prognostic marker. These results also indicate that CD133 as a single marker may not be sufficient for CSC identification in ccRCC and, therefore, more specific CSC markers should be developed.

AIMS: To study the pattern of expression and prognostic importance of c-erbB-2 protein in cervical carcinoma. METHODS: Sixty two cases of stage IB/IIA cervical carcinoma, representing the three main tumour types, were investigated immunohistochemically for the presence of c-erbB-2 protein expression, using a monoclonal antibody (CB11) to its internal domain. Follow up of at least five years' duration was available in all cases. RESULTS: Definite membrane staining was seen in 38.7% of cases. There was a strong correlation with poor survival (p less than 0.0001) particularly. For those with adenocarcinomas, this was the case when nodal metastases were present. In contrast, for squamous carcinomas and adenosquamous carcinomas, the association with a poor prognosis was most apparent in those patients without lymph node metastases. CONCLUSIONS: These findings raise the possibility that immunostaining for c-erbB-2 protein could be used as a prognostic marker and may help identify those patients for whom early adjuvant treatment might be beneficial.

Abnormalities of the tumour suppressor gene p53 have been shown in approximately 60% of advanced gastric adenocarcinomas and it has been suggested that the immunohistochemical finding of increased p53 expression is a prognostic marker in gastric cancer. No studies of early (T1) tumours have been reported. Over expression of p53 protein in 95 early gastric carcinomas and in adjacent mucosa was investigated using immunohistochemistry with antibody CM1. Thirty five per cent of the tumours were positive. The frequency of p53 positivity in tumours of tubular histological type (46%) was significantly higher than that in signet ring tumours (10%) (p = 0.006), and neoplasms that invaded deeply into the submucosa were more frequently positive (45%) than others (30%). Five of eight (62%) T1 tumours with lymph node metastases showed immunoreactive p53. In signet ring tumours, immunopositivity correlated with the frequency of DNA aneuploidy. p53 Over expression was also found in 15% of 26 examples of high grade dysplasia in mucosa adjacent to invasive tumours. No positivity was found in intestinal metaplasia or in normal mucosa. The findings show that immunocytochemically demonstrable over expression of p53 correlates with other morphological markers of aggressiveness in T1 gastric adenocarcinoma. The increasing frequency of p53 immunoreactivity in the sequence of high grade dysplasia-->early gastric cancer-->advanced gastric cancer supports the view that abnormalities of p53 are related to tumour progression in gastric carcinogenesis.

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Background

CD133 is known to be a cancer stem cell (CSC) marker. However, recent studies have revealed that CD133 is not restricted to CSC but to be expressed not only in human normal tissues but also in some cancers and could serve as a prognostic factor for the patients. Nevertheless, the expression of CD133 in human cholangiocarcinoma (CC) is rare and our study is to detect the expression and explore the potential functions of CD133 in human CC.

Methods

Fifty-nine cases, comprised of 5 normal liver tissues and 54 consecutive CC specimens (21 well-differentiated, 12 moderately-differentiated and 21 poorly-differentiated), were included in the study. Immunohistochemical stainning with CD133 protein was carried out, and statistical analyses were performed.

Results

CD133 was found to express in all 5 normal livers and 40 out of 54 (74%) CC tissues with different subcellular localization. In the well, moderately and poorly differentiated cases, the numbers of CD133 positive cases were 19 (19 of 21, 90%), 10 (10 of 12, 83%) and 11 (11 of 21, 52%) respectively. Further statistical analyses indicated that the expression and different subcellular localization of CD133 were significantly correlated with the differentiation status of tumors (P = 0.004, P = 0.009). Among 23 patients followed up for survival, the median survival was 4 months for fourteen CD133 negative patients but 14 months for nine CD133 positive ones. In univariate survival analysis, CD133 negative expression correlated with poor prognosis while CD133 positive expression predicted a favorable outcome of CC patients (P = 0.001).

Conclusions

Our study demonstrates that CD133 expression correlates with the differentiation of CC and indicates that CD133 is a potential indicator for differentiation and prognosis of human CC.