Dataset Information

The Role of AMACR, CD10, TMPRSS2-ERG, and p27 Protein Expression Among Different Gleason Grades of Prostatic Adenocarcinoma on Needle Biopsy.

ABSTRACT:

Objective

We examined the immunohistochemical expression of α-methyl acyl coenzyme A racemase (AMACR), CD10, TMPRSS2-ERG, and p27 in prostate adenocarcinoma tumors with different Gleason growth patterns and nonneoplastic prostate tissues to elucidate their roles in prostate carcinogenesis and histological aggressiveness.

Material and methods

In total, 80 archival core biopsy tissues diagnosed as prostate carcinoma, benign prostate hyperplasia, and atrophy cases were included. Immunoreactivity was evaluated by calculating the percentage of positively stained cells and the staining intensity. The mean values and test of significance were obtained using the Kruskal-Wallis test.

Results

We obtained mostly intense immunoreactivity for AMACR, CD10, and ERG in adenocarcinomas. Although no significant differences were noted regarding AMACR and ERG expression, samples with Gleason growth patterns 3 and 5 tended to be strongly positive for ERG. Pattern 3 tumors exhibited the weakest positivity for CD10. The p27 expression was strong and diffuse in nonneoplastic prostate tissues. The loss of p27 expression was more frequent for pattern 5 tumors.

Conclusion

ERG and AMACR were powerful markers to detect cancer. Especially, ERG is evident in early tumors may reflect its interaction with functional androgen receptors in cancer initiation. Pattern 5 tumors associated with stroma may have been exposed to more stromal substrates and upregulate their CD10 content as a protein degrader. We suggest that CD10 expression is associated with an increasing tumor grade. Decreased concentrations of p27 protein might be implicated in prostate carcinogenesis and may be a useful immunohistochemical adjunct in predicting histological aggressiveness.

SUBMITTER: Gulhan O

PROVIDER: S-EPMC8855389 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

The Role of AMACR, CD10, TMPRSS2-ERG, and p27 Protein Expression Among Different Gleason Grades of Prostatic Adenocarcinoma on Needle Biopsy.

Gülhan Özdemir Ö Mahi Balcı B

Clinical Medicine Insights. Oncology 20200804

<h4>Objective</h4>We examined the immunohistochemical expression of α-methyl acyl coenzyme A racemase (AMACR), CD10, TMPRSS2-ERG, and p27 in prostate adenocarcinoma tumors with different Gleason growth patterns and nonneoplastic prostate tissues to elucidate their roles in prostate carcinogenesis and histological aggressiveness.<h4>Material and methods</h4>In total, 80 archival core biopsy tissues diagnosed as prostate carcinoma, benign prostate hyperplasia, and atrophy cases were included. Immu ...[more]

PMID: 35185351

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Project description:Fusion of the TMPRSS2 prostate-specific gene with the ERG transcription factor is a putatively oncogenic gene rearrangement that is commonly found in prostate cancer tissue from men undergoing prostatectomy. However, the prevalence of the fusion was less common in samples of transurethral resection of the prostate from a Swedish cohort of patients with incidental prostate cancer followed by watchful waiting, raising the question as to whether the high prevalence in prostatectomy specimens reflects selection bias. We sought to determine the prevalence of TMPRSS2-ERG gene fusion among prostate-specific antigen-screened men undergoing prostate biopsy in the United States.We studied 140 prostate biopsies from the same number of patients for TMPRSS2-ERG fusion status with a fluorescent in situ hybridization assay. One hundred and thirty-four samples (100 cancer and 34 benign) were assessable.ERG gene rearrangement was detected in 46% of prostate biopsies that were found to have prostate cancer and in 0% of benign prostate biopsies (P < 0.0001). Evaluation of morphologic features showed that cribriform growth, blue-tinged mucin, macronucleoli, and collagenous micronodules were significantly more frequent in TMPRSS2-ERG fusion-positive prostate cancer biopsies than gene fusion-negative prostate cancer biopsies (P < or = 0.04). No significant association with Gleason score was detected. In addition, non-Caucasian patients were less likely to have positive fusion status (P = 0.02).This is the first prospective North American multicenter study to characterize TMPRSS2-ERG prostate cancer prevalence in a cohort of patients undergoing needle biopsy irrespective of whether or not they subsequently undergo prostatectomy. Our results show that this gene rearrangement is common among North American men who have prostate cancer on biopsy, is absent in benign prostate biopsy, and is associated with specific morphologic features. These findings indicate a need for prospective studies to evaluate the relationship of TMPRSS2-ERG rearrangement with clinical course of screening-detected prostate cancer in North American men, and a need for the development of noninvasive screening tests to detect TMPRSS2-ERG rearrangement.

Project description:BackgroundIn men with clinically localized prostate cancer who have undergone at least 1 previous negative biopsy and have elevated serum prostate-specific antigen (PSA) levels, long-term health outcomes associated with the assessment of urinary prostate cancer antigen 3 (PCA3) and the transmembrane protease, serine 2 (TMPRSS2):v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG) gene fusion (T2:ERG) have not been investigated previously in relation to the decision to recommend a repeat biopsy.MethodsThe authors performed a decision analysis using a decision tree for men with elevated PSA levels. The probability of cancer was estimated using the Prostate Cancer Prevention Trial Risk Calculator (version 2.0). The use of PSA alone was compared with the use of PCA3 and T2:ERG scores, with each evaluated independently, in combination with PSA to trigger a repeat biopsy. When PCA3 and T2:ERG score evaluations were used, predefined thresholds were established to determine whether the patient should undergo a repeat biopsy. Biopsy outcomes were defined as either positive (with a Gleason score of <7, 7, or >7) or negative. Probabilities and estimates of 10-year overall survival and 15-year cancer-specific survival were derived from previous studies and a literature review. Outcomes were defined as age-dependent and Gleason score-dependent 10-year overall and 15-year cancer-specific survival rates and the percentage of biopsies avoided.ResultsIncorporating the PCA3 score (biopsy threshold, 25; generated based on the urine PCA3 level normalized to the amount of PSA messenger RNA) or the T2:ERG score (biopsy threshold, 10; based on the urine T2:ERG level normalized to the amount of PSA messenger RNA) into the decision to recommend repeat biopsy would have avoided 55.4% or 64.7% of repeat biopsies for the base-case patient, respectively, and changes in the 10-year survival rate were only 0.93% or 1.41%, respectively. Multi-way sensitivity analyses suggested that these results were robust with respect to the model parameters.ConclusionsThe use of PCA3 or T2:ERG testing for repeat biopsy decisions can substantially reduce the number of biopsies without significantly affecting 10-year survival.

Dataset Information

The Role of AMACR, CD10, TMPRSS2-ERG, and p27 Protein Expression Among Different Gleason Grades of Prostatic Adenocarcinoma on Needle Biopsy.

Objective

Material and methods

Results

Conclusion

Publications

The Role of AMACR, CD10, TMPRSS2-ERG, and p27 Protein Expression Among Different Gleason Grades of Prostatic Adenocarcinoma on Needle Biopsy.

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