BACKGROUND Human bladder carcinoma is thought to arise from a field change that affects the entire urothelium. Whether independently transformed urothelial cell populations exist in the same patient is uncertain. METHODS We studied the clonality of urinary bladder carcinoma in 18 female patients who underwent cystectomy for urothelial carcinoma. None had multiple tumors. Tumor samples were obtained from different areas of the same tumor. Sixty‐seven tumor samples were analyzed. Tumor genomic DNA was microdissected and extracted from formalin‐fixed, paraffin‐embedded slides. The clonality of urothelial tumors was evaluated on the basis of a polymorphism of the X chromosome‐linked human androgen receptor gene (HUMARA) locus. The technique is dependent on digestion of DNA with the methylation‐sensitive restriction enzyme HhaI, polymerase chain reaction (PCR) amplification of HUMARA locus, and detection of methylation of this locus. With this method, only the methylated HUMARA allele is selectively amplified by PCR. RESULTS Eleven of 18 patients were informative. Nonrandom inactivation of the X chromosome was found in 9 of the 11 informative patients (82%). Seven patients showed different patterns of nonrandom X chromosome inactivation for tumor samples obtained from different regions of the same tumor. Two patients showed the same pattern of nonrandom X chromosome inactivation in all samples. CONCLUSIONS Some muscle‐invasive urothelial carcinomas may arise from independently transformed progenitor urothelial cells, supporting the “field effect” theory for bladder carcinogenesis. Cancer 2002;94:104–10. © 2002 American Cancer Society.

Background.—Cytokeratin 7 (CK7) and cytokeratin 20 (CK20) are 2 types of intermediate filament protein. Expression of CK7 is seen in the majority of primary urinary bladder carcinomas. CK20 is restricted to superficial and occasional intermediate cells of the normal urothelium of the bladder. Aberrant CK20 expression has been documented in urothelial carcinoma and has proved useful as an ancillary diagnostic aid for urinary bladder tumor. Our hypothesis is that the pattern of CK7 and CK20 expression in metastatic urothelial carcinoma duplicates the expression of the same markers in the primary tumors. Therefore, immunohistochemical staining of metastatic tumors for these 2 markers may be helpful for differential diagnosis in ambiguous metastatic tumor deposits. Objective.—To determine the concordance of CK7 and CK20 expression in primary bladder urothelial carcinoma and the matched lymph node metastasis. Design.—We studied 26 patients with lymph node metastases who underwent radical cystectomy and bilateral lymphadenectomy for bladder carcinoma. Immunohistochemical staining for CK7 and CK20 was performed on formalin-fixed paraffin-embedded tissues containing primary cancers and lymph node metastases. Results.—In all cases, there was a concordant expression of CK20 in the primary cancer and its matched lymph node metastasis. Twelve cases (46%) showed positive CK20 immunoreactivity in the primary tumor and its matched lymph node metastases, whereas 14 cases (54%) were negative for CK20 in both the primary tumor and lymph node metastasis. All cases showed positive CK7 immunoreactivity in the primary cancers and matched lymph node metastases. Conclusions.—CK20 immunoreactivity is reliably observed in metastases from bladder cancer when the primary tumor expresses CK20.

BACKGROUNDSome evidence suggests a role for HER‐2/neu overexpression in prostate carcinoma progression. Reported rates of HER‐2/neu overexpression in patients with prostate carcinoma vary greatly.METHODSThe authors studied radical prostatectomy specimens from 38 patients who had biochemical failure after undergoing radical prostatectomy for prostate carcinoma. Immunohistochemistry for HER‐2/neu overexpression using the HercepTest kit (Dako Corporation, Carpenteria, CA) was employed. Two different antigen‐retrieval techniques were used: 1) the standard U.S. Food and Drug Administration (FDA)‐approved HercepTest assay and 2) a modified HercepTest, which employed an alkaline citrate buffer, pH 9.0, for antigen retrieval and a 1‐hour primary antibody incubation time. The level of HER‐2/neu expression was evaluated on a scale from 0 (no staining) to 3+ according to the published guidelines. Fluorescent in situ hybridization for gene amplification was performed on all specimens.RESULTSWith the standard technique, only one specimen had 2+ staining, and no specimens had 3+ staining. With the modified technique, 10 specimens (26%) had 2+ staining, and 9 specimens (24%) had 3+ staining. There was a significant association between the level of HER‐2/neu expression shown with the modified technique and tumor stage (P = 0.03) as well as Gleason grade (P = 0.01). None of the specimens had HER‐2/neu gene amplification.CONCLUSIONSThe authors report a simple modification of the HercepTest that resulted in an increased rate of HER‐2/neu expression, which was correlated with poor‐risk pathologic findings. The findings suggest that adenocarcinoma of the prostate should be evaluated for HER‐2/neu expression with a prostate specific immunohistochemical procedure that differs from the FDA‐approved standard procedure. Cancer 2002;95:1650–5. © 2002 American Cancer Society.DOI 10.1002/cncr.10839

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