Álvaro S. Sarkis

Human papillomavirus DNA and p53 status in penile carcinomas.

Our study aimed at evaluating the presence of human papillomavirus (HPV) DNA in a series of 84 paraffin‐embedded (PET) penile carcinomas. We have also investigated the presence of p53 mutations in these tumors by immunohistochemistry (IHC), single‐stranded conformational polymorphism (SSCP) and DNA sequencing. Tissues were submitted to amplification of a 268 bp fragment from the β‐globin gene and a fragment of the E6 gene of HPV types 6, 11, 16 and 18. Twenty samples (18 fixed in Bouins solution and 2 in buffered formalin) were found inadequate and were excluded from the analysis. In the remaining 64 tumors, HPV DNA was found in 26% of the samples. The prevalence of HPV in fresh samples of the same tumors was 56%. The most prevalent type was HPV 16 in both fresh samples and PET. Isotopic in situ hybridization was performed in all PET samples, but only 2 cases were positive, 1 for HPV 16 and 1 for HPV 18. Immunohistochemistry with anti‐p53 pAb1801 antibody showed a positive nuclear reaction over more than 5% of tumor cells in 26% of the cases. SSCP of exons 5–8 of the p53 gene was performed on 9 HPV‐positive and 12 HPV‐negative specimens. Abnormal mobility was found in 26% of the tumors, of which 2 were HPV positive and 5 HPV negative. Point mutations were detected in p53 exons 6 (1 case), 7 (1 case) and 8 (5 cases), showing that high‐risk type HPVs and mutated p53 may coexist in these tumors. Our data indicate that a subset of penile carcinomas are etiologically related to HPV and that an overlapping subset may arise from mutational events in the p53 gene. Int. J. Cancer76:779–783, 1998.© 1998 Wiley‐Liss, Inc.

Microvascular tumour invasion in renal cell carcinoma: the most important prognostic factor.

To evaluate the role of microvascular invasion (MVI) in the primary lesion for predicting tumour behaviour in patients with renal cell carcinoma (RCC), as reliable clinical prognostic factors would be very valuable.

Androgen receptor CAG repeat polymorphism in prostate cancer from a Brazilian population

Shorter CAG repeats in the androgen receptor (AR) gene have been associated with increased prostate cancer risk. Aiming to investigate whether the AR CAG polymorphism is associated with an increased relative risk for prostate cancer in our population, genomic DNA from 133 prostate cancer patients and 279 healthy men controls were examined. We found no association between the AR CAG polymorphism and the relative risk of prostate cancer in white Brazilian individuals with a CAG repeat length </=21. Our results show that in the studied population the Asian-descendants have the highest, the white an intermediate and the black a tendency to the lowest CAG repeats rates. We observed a significant correlation between a lower number of CAG repeats and young age at diagnosis (P=0.034). This study is the first to investigate the association between the AR CAG repeat polymorphism and the relative risk of prostate cancer in the Brazilian population.

The Transcripts of SFRP1‚ CEP63 and EIF4G2 Genes Are Frequently Downregulated in Transitional Cell Carcinomas of the Bladder

Objective: The aim of the present study was to identify differentially expressed genes that might be associated with the phenotype of superficial and invasive bladder cancer. Methods: Differential display reverse transcriptase PCR (DDRT-PCR) was used to compare the expression pattern between normal bladder tissue and 4 groups of transitional cell carcinomas of the bladder regarding clinical stage and grade. Results: We were able to identify 72 different transcripts, of which 57 (79%) showed homology to known genes, 12 (17%) to hypothetical proteins and 3 (4%) to human expressed sequence tags. Among the differentially expressed genes, SFRP1,CEP63 and EIF4G2 were further validated by quantitative RT-PCR in a series of 50 transitional cell carcinomas. Overall, the transcripts of these three genes were shown to be downregulated in the bladder tumors analyzed. In accordance with the DDRT-PCR results, the SFRP1 transcripts were shown to be downregulated in 90% (45/50) of the bladder tumors as compared with the normal bladder tissue. Although EIF4G2 and CEP63 transcripts exhibited three different expression patterns, downregulation was found in about 50% of the cases analyzed. In addition, downregulation of both CEP63 and EIF4G2 gene transcription was associated with invasive tumors. Conclusion: The use of DDRT-PCR analysis to compare expression patterns among different subgroups of bladder tumors allowed us to identify a significant number of genes implicated in different cellular pathways that, when up- or downregulated, might play a role in the tumorigenic process of the bladder.

Identification of differentially expressed genes in prostatic epithelium in relation to androgen receptor CAG repeat length

The CAG repeat within exon 1 of the androgen receptor (AR) has been associated with the development of prostate cancer. The shorter number of glutamine residues in the protein has been associated with a higher transcriptional activity of the AR and increased relative risk for prostate cancer. In an attempt to identify differentially expressed genes in prostate cancer in relation to AR CAG repeat length variation, in this study we used total mRNA from normal and tumor tissues from 2 prostate cancer patients with AR alleles containing 19 and 26 CAG repeats to perform differential-display RT-PCR analysis. We were able to identify 48 different transcripts that showed homology to several known genes associated with different biological pathways. Among the differentially expressed genes, ATRX and SFRP1 were further validated by quantitative RT-PCR. The transcripts of both ATRX and SFRP1 genes proved to be down-regulated in most of the prostate tumors analyzed by quantitative RT-PCR. Hypermethylation of the promoter region of the SFRP1 gene was found in 17.5% (7/40) of the cases analyzed and was associated with the loss of SFRP1 expression (p=0.014). The differentially expressed genes identified in this study are implicated in several cellular pathways that, when up- or down-regulated, might play a role in the tumorigenic process of the prostate.

Benign glandular inclusion in obturator lymph node of a man treated for prostate carcinoma

Benign glandular inclusions in lymph nodes are extremely rare in men. Their identification is essential because it changes dramatically the prognosis and therapy of neoplasms. Described herein is the first case of benign glandular inclusion in an obturator lymph node dissected during a radical prostatectomy for treatment of prostate adenocarcinoma. A 60‐year‐old man underwent radical prostatectomy and obturator–hypogastric lymph node dissection for treatment of prostate adenocarcinoma. Benign glandular inclusion was found in microscopic examination. The lesion was characterized by two glandular spaces lined by a single, cuboid, benign epithelium localized in the sinus of one of four dissected lymph nodes. Immunohistochemistry showed mesothelial differentiation. Pathologists should be aware of benign glandular inclusion in obturator lymph nodes dissected during a radical prostatectomy for treatment of prostate cancer in order to avoid the incorrect diagnosis of metastatic disease.