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1.  Prostate cancer cell phenotypes based on AGR2 and CD10 expression 
The combination of expression patterns of AGR2 and CD10 by prostate cancer provided four phenotypes that correlated with clinical outcome. Based on immunophenotyping, CD10lowAGR2high, CD10highAGR2high, CD10lowAGR2low, and CD10highAGR2low were distinguished. AGR2+ tumors were associated with longer recurrence-free survival and CD10+ tumors with shorter recurrence-free survival. In high-stage cases, the CD10lowAGR2high phenotype was associated with a 9-fold higher recurrence-free survival than the CD10highAGR2low phenotype. The CD10highAGR2high and CD10lowAGR2low phenotypes were intermediate. The CD10highAGR2low phenotype was most frequent in high-grade primary tumors. Conversely, bone and other soft tissue metastases, and derivative xenografts, expressed more AGR2 and less CD10. AGR2 protein was readily detected in tumor metastases. The CD10highAGR2low phenotype in primary tumors is predictive of poor outcome; however, the CD10lowAGR2high phenotype is more common in metastases. It appears that AGR2 has a protective function in primary tumors but may have a role in the distal spread of tumor cells.
doi:10.1038/modpathol.2012.238
PMCID: PMC3638070  PMID: 23348903
Prostate cancer; AGR2; CD10; cancer cell phenotypes; patient stratification; bone and soft tissue metastases; xenografts
2.  Expression Levels of Estrogen Receptor Beta in Conjunction with Aromatase Predict Survival in Non-Small Cell Lung Cancer 
Estrogen signaling pathways may play a significant role in the pathogenesis of non-small cell lung cancers (NSCLC) as evidenced by the expression of aromatase and estrogen receptors (ERα and ERβ) in many of these tumors. Here we examine whether ERα and ERβ levels in conjunction with aromatase define patient groups with respect to survival outcomes and possible treatment regimens. Immunohistochemistry was performed on a high-density tissue microarray with resulting data and clinical information available for 377 patients. Patients were subdivided by gender, age and tumor histology, and survival data was determined using the Cox proportional hazards model and Kaplan-Meier curves. Neither ERα nor ERβ alone were predictors of survival in NSCLC. However, when coupled with aromatase expression, higher ERβ levels predicted worse survival in patients whose tumors expressed higher levels of aromatase. Although this finding was present in patients of both genders, it was especially pronounced in women ≥ 65 years old, where higher expression of both ERβ and aromatase indicated a markedly worse survival rate than that determined by aromatase alone. Conclusion: Expression of ERβ together with aromatase has predictive value for survival in different gender and age subgroups of NSCLC patients. This predictive value is stronger than each individual marker alone. Our results suggest treatment with aromatase inhibitors alone or combined with estrogen receptor modulators may be of benefit in some subpopulations of these patients.
doi:10.1016/j.lungcan.2011.03.009
PMCID: PMC3175023  PMID: 21511357
NSCLC; tissue microarray; aromatase; estrogen receptor; immunohistochemistry; prognosis
3.  Progesterone and estrogen receptor expression and activity in human non-small cell lung cancer 
Steroids  2011;76(9):910-920.
Lung cancer is the most common cause of cancer mortality in male and female patients in the US. Although it is clear that tobacco smoking is a major cause of lung cancer, about half of all women with lung cancer worldwide are never-smokers. Despite a declining smoking population, the incidence of non-small cell lung cancer (NSCLC), the predominant form of lung cancer, has reached epidemic proportions particularly in women. Emerging data suggest that factors other than tobacco, namely endogenous and exogenous female sex hormones, have a role in stimulating NSCLC progression. Aromatase, a key enzyme for estrogen biosynthesis, is expressed in NSCLC. Clinical data show that women with high levels of tumor aromatase (and high intratumoral estrogen) have worse survival than those with low aromatase. The present and previous studies also reveal significant expression and activity of estrogen receptors (ERα, ERβ) in both extranuclear and nuclear sites in most NSCLC. We now report further on the expression of progesterone receptor (PR) transcripts and protein in NSCLC. PR transcripts were significantly lower in cancerous as compared to non-malignant tissue. Using immunohistochemistry, expression of PR was observed in the nucleus and/or extranuclear compartments in the majority of human tumor specimens examined. Combinations of estrogen and progestins administered in vitro cooperate in promoting tumor secretion of vascular endothelial growth factor and, consequently, support tumor-associated angiogenesis. Further, dual treatment with estradiol and progestin increased the numbers of putative tumor stem/progenitor cells. Thus, ER- and/or PR-targeted therapies may offer new approaches to manage NSCLC.
doi:10.1016/j.steroids.2011.04.015
PMCID: PMC3129425  PMID: 21600232
Progesterone; Estrogen; Steroid hormone receptor; Non-small cell lung cancer; VEGF; Progenitor cells; Cancer stem cells; Angiogenesis

Results 1-3 (3)