Background Yes-associated protein (YAP) in the Hippo signaling pathway is a growth control pathway that regulates cell proliferation and stem cell functions. Abnormal regulation of YAP was reported in human cancers including liver, lung, breast, skin, colon, and ovarian cancer. However, the function of YAP is not known in prostate adenocarcinoma. The purpose of this study was to investigate the role of YAP in tumorigenesis, differentiation, and prognosis of prostate adenocarcinoma.
Methods The nuclear and cytoplasmic expression of YAP was examined in 188 cases of prostate adenocarcinoma using immunohistochemistry. YAP expression levels were evaluated in the nucleus and cytoplasm of the prostate adenocarcinoma and the adjacent normal prostate tissue. The presence of immunopositive tumor cells was evaluated and interpreted in comparison with the patients’ clinicopathologic data.
Results YAP expression levels were not significantly different between normal epithelial cells and prostate adenocarcinoma. However, YAP expression level was significantly higher in carcinomas with a high Gleason grades (8–10) than in carcinomas with a low Gleason grades (6–7) (p < .01). There was no statistical correlation between YAP expression and stage, age, prostate-specific antigen level, and tumor volume. Biochemical recurrence (BCR)–free survival was significantly lower in patients with high YAP expressing cancers (p = .02). However high YAP expression was not an independent prognostic factor for BCR in the Cox proportional hazards model.
Conclusions The results suggested that YAP is not associated with prostate adenocarcinoma development, but it may be associated with the differentiation of the adenocarcinoma. YAP was not associated with BCR.
Citations
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The effect of androgen in the development of the normal prostate and the evolution of benign prostatic hypertrophy (BPH), and prostatic adenocarcinoma has been proven. In addition to androgen, estrogen and progesterone are also thought to play a role in the pathogenesis of BPH and carcinoma. However, their exact roles are not yet known because there is no conclusive evidence. Thirty cases of prostatic adenocarcinoma and 16 cases of BPH were studied.
Immunohistochemical staining for estrogen receptor (ER) and progesterone receptor (PR) in epithelial and stromal cells, respectively was performed and the results were assessed semiquantitatively based on the number of positive cells per 100 total cells. Slides were scored as negative; less than 5% of cells, 1 ; 6~15% of cells, 2 ; 16~25% of cells, and 3 ; more than 26% of cells. The relationship between ER and PR expression and the patient's age, histologic grade, and clinical stage was evaluated in prostatic adenocarcinomas.
ER was negative in epithelial and in stromal cells for all prostatic adenocarcinomas and BPH cases. The PR expression in epithelial cells and in stromal cells of BPH was noted in 15 (93.8%) and 16 (100.0%) out of 16, respectively. The PR expression of carcinoma cells and stromal cells in prostatic adenocarcinoma was found in 28 (93.3%) and 23 out of 30 (76.7%), respectively. The PR immunoreactivities of stromal cells around carcinoma were 3 in 18 cases, 2 in one case, and 1 in 4 cases, but those of epithelial and stromal cells of BPH and carcinoma cells of prostatic carcinoma were similar to each other with a value of 3 in most cases. The PR expression rate of stromal cells around carcinoma was significantly correlated with the patient's age (p=0.044), but not with histologic grade and clinical stage. In summary, estrogen does not have a direct effect on the biological behavior of BPH and prostatic adenocarcinoma, but progesterone appears to play a role in the pathogenesis of BPH and prostatic adenocarcinoma. Further studies should clarify the biological role of progesterone in the human prostate.
Nuclear DNA content of 32 cases of prostate adenocarcinoma diagnosed 1986-1991 was determined by flow cytometry, with the use of paraffin-embedded archival tissue. The present study was done to define the relationship between clinical stage, histopathological grade, and DNA ploidy. Aneuploidy was found in 10(31.3%) cases including 7 cases of near-tetraploidy. Among diploid tumors, 36.4% were localized disease(stage A and B), 13.6% were characterized by invasion outside the prostate(stage C), and 50.0% showed distant metastasis(stage D). Among aneuploid tumors, 10.0% were stage B, 50.0% stage C, and 40.0% stage D. The degree of glandular differentiation was characterized by the Gleason score and the percentage of sampled tissue involved by carcinoma was graded by Dhom's method. Apparent correlation was found between Gleason grade and Dhom grade(P<0.05). All 13 tumors with a Gleason grade I(score of 2 to 5) were diploid. Four of 9 tumors with a Gleason grade II(score of 6 to 7) were aneuploid(near-tetraploidy 33.3%, aneuploidy 11.1%) and 60.0%, of tumors with a Gleason grade III(score of 8 to 10) were aneuploid(near-tetraploidy 40.0%, aneuploidy 20%). The percentage of aneuploid cases increased with advanced clinical stage, but the relationship between aneuploidy versus clinical stage was not significant.
However, it can be concluded that DNA ploidy correlates well with Gleason grade(p<0.05), which may have predictive prognostic value for prostate adeno-carcinomas.
The authors reviewed clinical data and 50 pathologic specimens from 41 patients of prostate adenocarcinoma filed in the Department of Pathology, Hanyang University school of Medicine, in order to evaluate correlation between clinical stages and histopathologic grades of prostate adenocarcinoma. Each of five currently used grading systems were compared with clinical stages of prostate adenocarcinomas. The followings results were obtained: All of the grading systems were relatively well correlated with clinical progression of the tumon. Histologic grading systems including Gleason's grading system, Gleasons scoring system and M.D. Anderson system showed better correlation than cytologic grading system of Mostofi. Gaeta gradings system regarding both histologic and cytologic aspects of the carcinoma showed good correlation to clinical stage with correlation coefficient of 0.654. Combined scoring system of cytologic and histologic grades (Mostofi-M.D. Anderson combined scoring system) showed better correlation to the clinical stage than single individual grading s system. The author conclued that Gleasons histologic grading system with cytologic characteristics of tumor cells would represent best parameter of clinical progression of the prostate adenocarcinoma.