J Pathol Transl Med.  2017 Jul;51(4):365-373. 10.4132/jptm.2017.05.04.

Yes-Associated Protein Expression Is Correlated to the Differentiation of Prostate Adenocarcinoma

• Noh MG
• Kim SS
• Hwang EC
• Kwon DD
• Choi C

• KMID: 2392576
• DOI: http://doi.org/10.4132/jptm.2017.05.04

Abstract

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.

Keyword

Yes-associated protein (YAP); Prostate adenocarcinoma; Immunohistochemistry; Gleason score

MeSH Terms

Adenocarcinoma*
Breast
Carcinogenesis
Cell Proliferation
Colon
Cytoplasm
Epithelial Cells
Humans
Immunohistochemistry
Liver
Lung
Ovarian Neoplasms
Prognosis
Proportional Hazards Models
Prostate*
Prostate-Specific Antigen
Recurrence
Skin
Stem Cells
Tumor Burden
Prostate-Specific Antigen

Figure

• 

  Fig. 1. Scoring according to the expression of Yes-associated protein (YAP) in prostate adenocarcinoma. (A) In prostate adenocarcinoma, both nuclei and cytoplasm are strongly positive for YAP, scored as high. (B) Negative expression is noted for YAP in prostate adenocarcinoma cells, which is scored as negative. (C) Nuclear expression in prostate adenocarcinoma cells, the nuclear stain over one tenth is scored as high. (D) YAP expression in normal prostate glands. Basal cells are strongly positive which were used as a positive control. Luminal cells did not show YAP expression. Stromal cells reveal mild expression of YAP.

• 

  Fig. 2. Expression of Yes-associated protein (YAP) in prostate adenocarcinoma and normal prostate glands. (A–D) Hematoxylin and eosin (H&E)–stained section of benign glands and immunohistochemical stain of YAP in normal prostate glands. Luminal cells of normal prostate gland show no expression to mild expression of YAP in the cytoplasm. All of the basal cells and stroma show positive YAP. H&E-stained section of well-to-moderately differentiated prostate adenocarcinoma (Gleason score, 4 + 3= 7). There are poorly formed glands and a few well-formed glands. (F) Expression of YAP in well-to-moderately differentiated prostate adenocarcinoma (Gleason score, 4+3=7). Tumor cells show either no or mild expression in the cytoplasm. (G) H&E-stained section of poorly differentiated prostate adenocarcinoma (Gleason score, 5+5=10). (H) Tumor cells display strong positivity in both nuclei and cytoplasm.

• 

  Fig. 3. Kaplan-Meier estimates of biochemical recurrence. Graph of the curve for progression-free survival in prostate adenocarcinoma patients, according to Yes-associated protein (YAP) expression (p=.02).

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