Distinguishing prostatic from colorectal adenocarcinoma on biopsy samples: the role of morphology and immunohistochemistry.
ABSTRACT Poorly differentiated carcinoma on prostate or colorectal biopsy can occasionally present a diagnostic challenge in determining tumor source especially in locally advanced colorectal carcinoma (CRCa) or prostate carcinoma (PCa). Such determination can affect prognosis and therapy.
To evaluate the role of morphology and immunohistochemistry in the previously mentioned setting.
Surgical pathology and consultation records. Hematoxylin-eosin sections were reviewed in 16 cases (11 PCa, 5 CRCa). Immunohistochemistry for 9 markers was performed in 15 cases.
Dirty necrosis, seen in 5 (100%) of 5 CRCa and 2 (18%) of 11 PCa cases, and the presence of columnar cells with basal nuclei, seen in 5 (100%) of 5 CRCa and 1 (9%) of 11 PCa cases, appear to be the most useful morphologic parameters. Immunohistochemistry confirmed the value of prostate-specific antigen (PSA), CDX2, cytokeratin (CK) 20, and beta-catenin in the differential of CRCa (0% PSA+, 60% CDX2+, 80% CK20+, and 100% beta-catenin+) versus PCa (80% PSA+, 0% CDX2+, 10% CK20+, and 0% beta-catenin+). P501S had a similar sensitivity as PSA in detecting PCa (80%). Two (20%) of 10 PCa cases were positive for 1 of the 2 markers but not the other. P501S was negative in all 5 cases of CRCa.
P501S is a useful marker in this setting when included together with PSA, CDX2, CK20, and beta-catenin. P501S labels a subset of PCa cases that are negative for PSA. Dirty necrosis and/or columnar cells with basal nuclei could also be of help.
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ABSTRACT: Prostate cancer patients with rectal involvement are rare, and the factors associated with the survival of these patients are yet to be elucidated.Patients and methods: We collected data on patients who were admitted to our hospital for prostate cancer in the last thirteen years and of those in studies in the literature. The associations of clinical characteristics with survival were evaluated using Cox regression models. This study included 94 patients (5 admitted to our hospital and 89 from studies in the literature) of prostate cancer with rectal involvement. 11 patients in the group of synchronous rectal involvement at first cancer diagnosis (n = 58) and 23 patients in the group of metachronous diagnosis of rectal involvement (n = 29) died at the latest follow up. The estimated overall survival rate (% +/- SE) at 1, 3, and 5 years were 68.3 +/- 5.3%, 54.4 +/- 7.2%, and 38.1 +/- 11.1%, respectively. In the Cox univariate analysis, Asian prostate cancer (p = 0.001) was associated with better survival, while rectal bleeding (p = 0.043), metachronous presentation of development of rectal involvement (p = 0.000), prior hormonal therapy (p = 0.000) and extrarectal metastases (p = 0.054) were associated with poor survival. In multivariate analysis, prior hormone therapy (HR = 14.540, p = 0.000) and rectal bleeding (HR = 2.195, p = 0.041) retained independent poor prognostic values. There were 13 patients survived for more than 3 years, the longest survival time was 96 months. Total pelvic extenteration (TPE) combined with hormonal therapy in 12 hormone-untreated prostate cancer give us six of thirteen long-term survivors for more than 3 years in this series. Our findings suggest that rectal involvement does not necessarily predict a worse outcome when presenting as a previously hormone-untreated disease and that the prognosis was worse when presenting as a hormone relapsed disease. Prior hormone therapy and rectal bleeding were associated independently with a significantly poor overall survival in prostate cancer patients with rectal involvement. TPE combined with hormonal therapy appears to confer better overall survival in hormonally untreated patients.Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1604504118106105.Diagnostic Pathology 02/2014; 9(1):35. DOI:10.1186/1746-1596-9-35 · 2.41 Impact Factor
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ABSTRACT: The following are the International Society of Urological Pathology (ISUP) recommendations for the use of immunohistochemistry (IHC) in prostate specimens. Either high-molecular weight cytokeratin (34βE12 or CK5/6 or others) or p63 or a combination of the 2 with AMACR either in a double or triple cocktail is recommended for the workup of small foci of atypical glands suspicious for adenocarcinoma of the prostate (PCa). ERG is optional as it is present in only 40% to 50% of prostate cancers and also positive in high-grade prostatic intraepithelial neoplasia. In the setting of obvious carcinoma or benign glands, there is no justification to do basal cell stains and AMACR. If there is a Gleason score of 3+4=7 or a higher-grade cancer on at least 1 part, the workup of other parts with an atypical focus suspicious for Gleason score 3+3=6 cancer is not recommended. In the setting of Gleason score 4+3 or 4+4=8 cancer on at least 1 part, the extent of high-grade cancer could affect clinical treatment such that workup of other atypical possible high-grade cancer foci is justified. In the setting of Gleason score 4+3 or higher-grade cancer on at least 1 part, given that intraductal carcinoma in the vast majority of cases is considered extension of high-grade cancer into prostatic ducts and acini, it is not recommended in the setting of definitive invasive high-grade cancer that workup of additional cribriform lesions be pursued. In the setting of Gleason score 3+3 on at least 1 part, the number of positive cores and/or their location could possibly affect subsequent therapy in terms of suitability for active surveillance or focal therapy, such that unless one knows with certainty that it would not affect therapy, it is justified to perform an IHC workup of additional atypical foci. In the differential diagnosis of high-grade PCa versus urothelial carcinoma (UC), the primary option is to use prostate-specific antigen (PSA) as a first test to identify PCa and GATA3 to identify UC. If GATA3 is not available, then HMWCK and p63 can be used. If the tumor is PSA positive with intense staining and HMWCK and p63 negative, the findings are diagnostic of PCa. If the tumor is equivocal/weak/negative for PSA and negative/focal for p63 and HMWCK, then one needs to perform staining for P501S, NKX3.1, and GATA3. Some experts also include PAP in this second round of staining. If the tumor is negative for PSA and diffusely strongly positive for p63 and HMWCK, the findings are diagnostic of UC. If the tumor is negative for PSA and moderately to strongly positive for GATA3, it is diagnostic of UC. Laboratories should be encouraged to use GATA3 for UC and add P501S and NKX3.1 as prostate markers in addition to PSA, p63, and HMWCK. If GATA3, p501S, and NKX3.1 are not available in equivocal cases, the case should be sent out for consultation to laboratories with these antibodies. The article also covers the use of IHC in: (1) high-grade PCa versus bladder adenocarcinoma; (2) prostatic small cell carcinoma versus high-grade PCa; (3) metastatic carcinoma of unknown primary: rule out PCa; (4) nonspecific granulomatous prostatitis/xanthoma versus high-grade PCa; (5) adult prostate sarcoma versus sarcomatoid PCa; (6) colorectal adenocarcinoma versus high-grade PCa; and (7) prognostic IHC markers.
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ABSTRACT: Prostate-specific antigen (PSA) levels are affected by non-cancerous conditions such as benign prostatic hyperplasia, inflammations, and inherited factors. To search for genetic variants associated with PSA levels, we conducted a genome-wide association study (GWAS) using a two-stage design. A total of 554 men from the Korean Cancer Prevention Study-II were used as a discovery stage and 1575 men collected by the Korean Genome Epidemiology Study were used as a replication stage. Analysis by Genome-wide Human single-nucleotide polymorphism (SNP) array 5.0 was performed by using DNAs derived from venous blood. We analyzed the association between genetic variants and PSA levels using multivariate linear regression models, including age as a covariate. We detected 12 genome-wide significant signals on chromosome 1q32.1, 10q11.2, and 19q13.41 between PSA levels and SNPs. The top SNP associated with log PSA levels was rs2153904 in SLC45A3 (p values, 5.24×10(-9) to 2.00×10(-6)). We also investigated GWAS using 754 subjects from KCPS-II cohort whether our genome-wide significant loci were associated with a risk of prostate cancer (PCa) (200 PCa cases and 554 controls). Three of the SNPs on 10q11.2, rs7077830, rs2611489, and rs4631830, were associated with a risk of PCa. However, two loci, 1q32.1 and 19q13, were not significantly associated with a PCa risk. We suggest that our results for some but not all PCa risk SNPs to be associated with PSA levels could be used as an evidence for the advance of individual PCa screening strategies, such as applying a personalized cutoff value for PSA. Copyright © 2014. Published by Elsevier B.V.Gene 11/2014; 556(2). DOI:10.1016/j.gene.2014.11.059 · 2.08 Impact Factor