This report discusses six issues that affect the measurement of disparities in health between groups in a population:
Selecting a reference point from which to measure disparityMeasuring disparity in absolute or in relative termsMeasuring in terms of favorable or adverse eventsMeasuring in pair-wise or in summary fashionChoosing whether to weight groups according to group sizeDeciding whether to consider any inherent ordering of the groups.
These issues represent choices that are made when disparities are measured.
Examples are used to highlight how these choices affect specific measures of disparity.
These choices can affect the size and direction of disparities measured at a point in time and conclusions about the size and direction of changes in disparity over time. Eleven guidelines for measuring disparities are presented.
Choices concerning the measurement of disparity should be made deliberately, recognizing that each choice will affect the results. When results are presented, the choices on which the measurements are based should be described clearly and justified appropriately.
Disparity; Statistics; Race; Hispanic origin
Myxoid liposarcoma is a subtype of liposarcoma. This specific subtype can be identified based on its characteristic histological and cytogenetical features. The tumor has a fusion transcript of the CHOP and TLS genes, which is caused by t(12;16)(q13;p11). Most of the fusion transcripts that have been identified fall into three categories, specifically type I (exons 7-2), type II (exons 5-2), and type III (exons 8-2). A total of seven myxoid liposarcomas associated with the rare phenomenon of cartilaginous differentiation have been documented in the literature. Currently, only one of these cases has been cytogenetically analyzed, and the analysis indicated that it was a type II TLS-CHOP fusion transcript in both the typical myxoid liposarcoma and cartilaginous areas. This study presents a second report of myxoid liposarcoma with cartilaginous differentiation, and includes a cytogenetical analysis of both the myxoid and cartilaginous areas.
Liposarcoma, myxoid; Cartilaginous differentiation; Cartilage; Heterologous component; TLS/CHOP fusion transcript
The epidermal growth factor receptor (EGFR) is a surrogate marker for basal-like breast cancer. A recent study suggested that EGFR may be used as a target for breast cancer treatment.
A total of 706 invasive ductal carcinomas (IDC) of the breast were immunophenotyped, and 82 cases with EGFR protein expression were studied for EGFR gene amplification.
EGFR protein was expressed in 121 of 706 IDCs (17.1%); 5.9% were of luminal type, 25.3% of epidermal growth factor receptor 2 (HER-2) type, and 79.3% of basal-like tumors. EGFR gene amplification and high polysomy (fluorescent in situ hybridization [FISH]-positive) were found in 18 of 82 cases (22.0%); 41.2% of the HER-2+, EGFR+, cytokeratin 5/6- (CK5/6-) group, 11.2% of the HER-2-, EGFR+, CK5/6- group, and 19.1% of the HER-2-, EGFR+, CK5/6+ group. FISH-positive cases were detected in 8.3% of the EGFR protein 1+ expression cases, 15.9% of 2+ expression cases, and 38.5% of 3+ expression cases. In group 2, the tumors had a high Ki-67 labeling (>60%), but the patients showed better disease-free survival than those with tumors that co-expressed HER-2 or CK5/6.
EGFR-directed therapy can be considered in breast cancer patients with EGFR protein overexpression and gene amplification, and its therapeutic implication should be determined in HER-2 type breast cancer patients.
Breast neoplasms; Receptor, epidermal growth factor; Gene amplification; Protein expression
Hypermethylation of the tumor suppressor genes is frequently observed in the tumor development and progression. However, the correlation between the hypermethylation of the tumor suppressor genes, CDH1 and the axillary lymph node (ALN) metastasis is not fully elucidated. To verify the role of the CDH1 promoter hypermethylation in the ALN metastasis and prognosis, we compared the methylation status of the CDH1 genes in the primary lesion and the paired metastatic ALNs.
We selected a total of 122 paraffin-embedded specimens of the primary and paired metastatic lymph node from 61 breast cancer patients and analyzed the frequency of hypermethylation in the primary and metastatic lymph node using the methylation-specific polymerase chain reaction. In addition, the methylation status of CDH1 was analyzed with the clinicopathologic characteristics, the disease-free survival and disease-specific survival.
The hypermethylation of CDH1 gene was identified in 54 (88.5%) of the 61 patients who had axillary metastasis. The hypermethylation status of the CDH1 gene was significantly increased in the metastatic ALNs compared with that in the primary tumors (60.7% vs. 45.9%, p<0.001). The hypermethylation status of the CDH1 genes in the metastatic ALNs was associated with a poor histologic grade (p=0.041) and the patients who had methylated tumor in the primary lesion showed worse disease-free survival than the patients who did not have methylated tumor (p=0.046).
This study suggests that hypermethylation of the CDH1 gene may play a pivotal role in the metastasis of the axillary lymph node and the breast cancer recurrence.
Breast neoplasms; Lymph nodes; Methylation; Recurrence; Tumor suppressor genes
Extranodal natural killer (NK)/T-cell lymphoma is a subtype of lymphoma that is derived from NK cells. It is considered as an aggressive form of non-Hodgkin's lymphoma because of frequent relapses and resistance to treatment. Relapsed NK/T-cell lymphoma often follows a fulminant course that is refractory to conventional chemotherapy treatment.
Several patients with extranodal NK/T-cell lymphoma showed long-term survival in spite of frequent relapses. Thus, the medical records of patients diagnosed with extranodal NK/T-cell lymphoma from 1995 to 2007 were reviewed and assessed.
Of the 140 cases reviewed, 6 were selected (4.29%). Each of these patients had a minimum of 3 relapses or disease progression during the follow-up period, and their median overall survival was 66 months (range, 42-89 months). They were grouped according to the atypical clinical behavior observed: (1) repeated relapses or progression (≥3 times) during follow-up; and (2) long-term survival of more than 40 months, as the longest overall survival median was previously considered at approximately 40 months. The clinicopathological and laboratory characteristics of these patients were similar to those of other extranodal NK/T-cell lymphoma patients. However, 5 of the studied cases involved relatively lower expression of the proliferation-related antigen Ki-67 (<40-50%), indicating less proliferative activity. Clinically, they showed delayed relapse for at least 20 months after the initial complete remission.
Our observations suggest that the clinical behavior of some extranodal NK/T-cell lymphoma patients differs from the typical clinical course.
Extranodal NK/T-cell lymphoma; Relapse; Survival; Indolent
Immunohistochemical staining for p16INK4a and Ki-67 has been used to improve the accuracy in making a diagnosis of the uterine cervix cancer on biopsy. This study was conducted to examine the usefulness of these markers in the pathological diagnosis based on cervical biopsy.
We selected a consecutive series of 111 colposcopically directed cervical punch biopsies. Using these biopsy samples, we performed an immunohistochemical staining for p16INK4a and Ki-67 to establish a diagnosis. The slides were circulated among four pathologists in a sequential order: the hematoxylin and eosin (H&E) slide, H&E slide and p16INK4a-stained slide, and H&E slide, p16INK4a- and Ki-67-stained slides.
The overall rates of the concordance in the first, the second, and the third diagnoses were 77.5%, 82.0%, and 82.0%, respectively. The rate of the concordance in the diagnosis of cervical intraepithelial neoplasm (CIN) 2/3 was increased from 62.2% to 73.0%. But there was a variability in the rate of the revision of the diagnosis between the pathologists. With the application of criteria for interpreting the expressions of p16INK4a and Ki-67, benign and CIN 1 lesions showed a p16INK4a expression score of 0 or 1. But CIN 2 and CIN 3 lesions showed a p16INK4a expression score of 2 and 3, respectively.
The immunostain for p16INK4a and Ki-67 might be useful in reducing an inter-observer variability. But criteria for interpreting both markers should be strictly applied.
Uterine cervix; p16INK4a; Ki-67
Mantle cell lymphoma (MCL) is a relatively rare subgroup of non-Hodgkin's lymphoma that is characterized by an aggressive and severe disease course with frequent involvement of regional lymph nodes and/or early metastasis. Because most cases of MCL are diagnosed in the advanced stages, clinical data on extranodal or early stage MCL is lacking, and MCL that is both extranodal and diagnosed during the early stages is even more rare. There have been several case reports on primary gastric MCL, which comprise a type of extranodal MCLs. However, to our knowledge, there have been no reports on solitary primary gastric MCL without regional lymph node involvement or distant metastasis. Recently, the authors experienced an uncommon case of MCL with the aforementioned characteristics that was managed with chemotherapy followed by allogenic stem cell transplantation.
Mantle cell lymphoma; Stomach; Primary; Solitary, Cyclin D1 positive
Among more than 500 microRNAs, microRNA-21 (miR-21) is known to act as an oncogene. The aim of this study was to investigate the significance of miR-21 expression level in relation with clinicopathological factors and prognosis in breast cancer.
MicroRNA was extracted from cancer and normal breast tissue of 109 breast cancer patients who underwent surgery from 2002 to 2004 using the Taqman® MicroRNA Assay. The correlation between miR-21 expression and clinicopathologic features was analyzed and the significance of miR-21 as a prognostic factor and its relationship with survival was determined.
MiR-21 expression was higher in cancer tissues than in normal tissues (p<0.0001). High miR-21 expression was associated with mastectomy, larger tumor size, higher stage, higher grade, estrogen receptor (ER) negative, human epidermal growth factor receptor 2 (HER2) positive, HER2 positive breast cancer subtype, high Ki-67 expression, and death. On multivariate analysis, prognostic factors for overall survival were ER and miR-21. High miR-21 expression was significantly related to lower overall survival (p=0.031).
This study supports the role of miR-21 as an oncogene and a biomarker for breast cancer with its high expression in cancer tissues and its relationship with other prognostic factors and survival.
Breast neoplasms; Human MicroRNA-21; Oncogene; Prognosis; Survival
We report here on the multiple genital tract neoplasms in a 41-yr-old Korean woman with Peutz-Jeghers Syndrome (PJS). The patient presented with lower abdominal pain. Her previous medical history was PJS and breast cancer. Pelvic ultrasound showed a multilocular cyst at the right adnexal region, diagnosed as bilateral ovarian mucinous borderline tumors. An ovarian sex cord tumor with annular tubules was incidentally diagnosed together with a minimal deviation adenocarcinoma of the uterine cervix and mucinous metaplasia of both the Fallopian tubal mucosa and the endometrium. Although the cases of multiple genital tract tumors with PJS has rarely been reported, the present case appears to be the first in Korea in which the PJS syndrome was complicated by multiple genital tract tumors and infiltrating carcinoma of the breast. The clinical significance of the multiple genital tract tumors and breast cancer associated with PJS is reviewed.
Peutz-Jeghers Syndrome; Breast; Ovary; Cervix Uteri; Fallopian Tubes
The metastasis-suppressing role of the nm23 gene in the metastatic spread of malignant tumor is still debated. We examined the nm23-H1 protein expression and gene mutation in non-Hodgkin's lymphomas to compare with the clinicopathologic parameters. The expression of nm23-H1 protein was immunohistochemically examined in 150 cases of non-Hodgkin's lymphomas; 85 diffuse large B cell lymphomas (DLBCL), 18 marginal zone B cell lymphomas (MZL), 3 mantle cell lymphomas, 25 peripheral T cell lymphomas, not otherwise specified (TCLNOS), and 19 NK/T cell lymphomas (NK/T). Eighty-one cases (58 DLBCL, 6 MZL, 4 TCLNOS, and 13 NK/T) were studied for nm23-H1 gene mutation in exon 1 to 5. The high expression of nm23-H1 protein was associated with the high IPI score (p=0.019) and the low survival rate of the patients (p=0.0039). The gene mutation of nm23-H1 was detected in 10.3% of DLBCL and 30.7% of NK/T; but none in MZL and TCLNOS. The mutation was found in exon 1 in 5 cases, exon 2 in two cases, exon 4 in one case and both exon 1 and 2 in two cases. Our results suggest that the expression of nm23-H1 protein can be used as a poor prognostic marker in non-Hodgkin's lymphomas, and the mutational change of gene may operate in the lymphomagenesis.
nucleoside diphosphate kinase A; nm23-H1 Protein; Lymphoma, Non-Hodgkin; Mutation; Prognosis
Methylation of p16 is an important mechanism in cervical carcinogenesis. However, the relationship between cervical squamous cell carcinoma (SCC) and Epstein-Barr virus (EBV) remains controversial. Here, we explored whether EBV infection and/or p16 gene inactivation would play any role in cervical carcinogenesis. Eighty-two specimens included 41 invasive SCCs, 30 cervical intraepithelial neoplasm (CIN; CIN 1, 11 cases, CIN II, 3 cases, CIN III 16 cases) and 11 nonneoplastic cervices. EBV was detected by polymerase chain reaction (PCR) for EBNA-1 and in situ hybridization for EBER-1. The p16 methylation-status and the expression of p16 protein were studied by methylation-specific PCR and immunohistochemistry, respectively. The materials were divided into four groups: 1) nonneoplastic cervices, 2) CIN I, 3) CIN II-III and 4) invasive SCCs. p16 methylation and p16 immunoexpressions increased in CIN and invasive SCCs than nonneoplastic tissue. p16-methylation and p16-immunoreactivities were higher in the EBV-positive group (p=0.009, p<0.001) than in the EBV-negative group. EBV was detected more frequently in CIN and SCCs than nonneoplastic cervices. In conclusion, a correlation between p16 methylation, p16 immunoreactivity and the detection of EBV strongly suggested that the cooperation of EBV and p16 gene may play a synergic effect on cell cycle deregulation.
Protein p16; Methylation; Herpesvirus 4, Human; Epstein-Barr Virus Infections; Cervix Neoplasms; Carcinogenesis
Hybrid carcinoma of the salivary gland is a very rare entity that has been described only in the parotid and palate. The occurrence of a hybrid carcinoma of maxillary sinus has not been reported. The diagnosis of hybrid carcinoma is important particularly when the components of tumor have different biologic behaviors. Diagnosis and treatment require a high index of suspicion, especially when the tumor is an epithelial-myoepithelial carcinoma, pathological effort to look for a more aggressive accompanying tumor, and proper oncologic treatment. We describe a case of 26-yr-old woman with a hybrid carcinoma composed of epithelial-myoepithelial carcinoma with an adenoid cystic carcinoma component (cribriform pattern) in the right maxillary sinus with a brief review of the relevant literature.
Hybrid; Carcinoma; Maxillary Sinus Neoplasms; Carcinoma, Adenoid Cystic
The Pax5 gene encodes the B-cell-specific activator protein which is a key regulator in development and differentiation of B-cell. We studied the expression of Pax5 in hematologic malignancies to evaluate the diagnostic utility as a B cell marker. Materials included 70 B cell lymphomas, 26 T cell lymphomas, 53 acute leukemias, and 6 multiple myelomas (MMs). Representative areas from the paraffin embedded tissues were selected for tissue microarray, and the expressions of Pax5 was immunohistochemically evaluated. Pax5 was strongly expressed in most of the B cell lymphomas; 44 of 47 diffuse large B cell lymphomas (93.6%), 15 of 16 marginal zone B cell lymphomas (93.8%), all 3 mantle cell lymphomas, 2 follicular lymphomas, and 2 Burkitt's lymphomas (100%). However, Pax5 was expressed in only one of 26 T cell lymphomas. Among leukemias, it was expressed in 10 of the 14 B acute lymphocytic leukemias (ALLs) (72.4%), but also in 3 of the 6 T ALLs (50%), 13 of the 26 acute myelogenous leukemias (AMLs) (50%) and in all 3 ALL arising in chronic myelogenous leukemias and 4 mixed B ALL and AML. In MMs, Pax5 was negative in all cases. We concluded that Pax5 is very useful B cell marker in classification of lymphomas, but not of acute leukemias.
Most of malignant tumors arising in ovarian and extraovarian endometriosis are carcinomas. Mixed mullerian tumor and endometrial stromal sarcoma arising in intestinal endometriosis are rarely described, but its clinicopathologic features have not been well characterized. Here we report a case of endometrial stromal sarcoma of the sigmoid colon arising in endometriosis with a review of six additional cases of endometrial stromal sarcoma arising in intestinal endometriosis found in English literatures. The patients ranged in age from 36 to 64 yr. Presenting symptoms were pain, bloody diarrhea, and tenesmus. Some patients had a previous history of endometriosis. Most of the tumors arose in the rectosigmoid colon. The histologic features were the same as their uterine counterpart. No death of disease had been reported. This rare tumor should not be confused with gastrointestinal stromal tumor clinically and histologically.