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T Nazeer

Publications and source records attributed to T Nazeer.

26 records · Page 2Linked to original sources

Quantitative immunohistochemical determination of cathepsin D levels in prostatic carcinoma biopsies. Correlation with tumor grade, stage, PSA level, and DNA ploidy status.

National screening programs resulting in an increased detection rate of prostatic adenocarcinoma have prompted the search for new methods of predicting disease outcome that can be applied to the initial narrow bore needle biopsy specimens. Cathepsin D, a lysosomal aspartyl protease and autocrine mitogen, has been studied in a wide variety of human neoplasms as an invasion and metastasis marker. Prostatic carcinoma needle biopsy tumor cell cathepsin D content was measured in 61 men using a semiquantitative image analysis assisted immunohistochemical procedure. Results were compared with preoperative serum prostatic specific antigen levels, tumor grade, DNA ploidy status, pathologic stage after radical prostatectomy and disease recurrence during a median 2.6 year follow-up. Biopsy cathepsin D levels significantly correlated with tumor grade (P = .022) and DNA ploidy status (P = .028) by logistic regression analysis. Post-prostatectomy pathologic stage and disease recurrence did not correlate with tumor cathepsin D levels. Final prostatectomy grade and DNA ploidy status independently predicted metastasis and post-operative disease recurrence (P < .001). Although this study did not find independent prognostic status for cathepsin D in prostate cancer, the correlation with tumor grade and DNA ploidy status is noteworthy and the inter-relationship of outcome variables may prove of interest and warrant further evaluation of this potential predictor or CO-predictor of disease outcome.

Adenocarcinoma↗

E-cadherin expression in prostatic carcinoma biopsies: correlation with tumor grade, DNA content, pathologic stage, and clinical outcome.

We compared tumor grade and DNA content with expression of E-cadherin (E-CD), a cell adhesion molecule associated with cell-cell and cell-matrix interaction, leukocyte function, and tumor invasion and metastases, on 56 prostate carcinoma needle biopsies. The findings were correlated with final pathologic stage at subsequent prostatectomy, preoperative serum prostate-specific antigen level and further development of metastases during an initial 2.4-yr mean clinical follow-up period (range 0.5 to 5.5 yr). E-CD expression (uvomorulin, L-CAM, cell CAM 80/120, ARC-1, Sigma, St. Louis, MO) was measured by double-linked immunoalkaline phosphatase immunohistochemistry quantified with a the Roche RPW image analyzer (Roche Image Analysis Systems, Elon College, NC). DNA ploidy was determined on formalin-fixed, paraffin-embedded Feulgen-stained 5-microns tissue sections of the narrow-bore initial prostate carcinoma biopsies with the Roche RPW image analyzer. The 51% mean positive area E-CD expression in the group of 56 adenocarcinomas was significantly less than the 76% expression level for 15 normal control prostate tissues (P < 0.001). E-CD expression was also decreased in aneuploid (39%) versus diploid tumors (54%, P < 0.001); and in high-grade (44%) versus low-grade lesions (54%; P < 0.01). The 44% E-CD expression level in patients with metastases was lower than the 52% level in the nonmetastatic cases, but this finding was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Cadherins↗

Comparative quantitative immunohistochemical and immunoradiometric determinations of cathepsin D in endometrial adenocarcinoma: predictors of tumor aggressiveness.

Previous comparisons of results of biochemical and immunohistochemical assays for Cathepsin D protease (CD) have conflicted in breast tumors and have not been applied to endometrial adenocarcinomas. We studied CD levels in 31 endometrial adenocarcinomas comparing immunoradiometric assay (IRA) of tumor cytosol with quantitative immunohistochemistry (QIH). Corresponding formalin-fixed paraffin-embedded sections were stained with a polyclonal antibody and measured with the CAS 200 Image Analyzer using a modified cytoplasmic antigen quantification program. Significant and trended increases in CD levels by IRA and QIH were similarly seen in high-grade tumors (IRA p < 0.001; QIH p < ns), papillary serous carcinoma subtype, and cases with deep myometrial invasion (IRA p < 0.005; QIH p < 0.04). Higher mean CD levels by QIH correlated significantly with positive lymph node status (LN+ 0.18 U/cell; LN- 0.09 U/cell; p < 0.03). No correlation of CD by IRA or QIH with estrogen- and progesterone-receptor tumor status was seen. We conclude that image quantification immunohistochemistry is an objective and sensitive method for determining tumor CD levels, CD by QIH directly correlates with standard prognostic indicators such as myometrial invasion and lymph node metastasis, and CD by QIH may prove clinically useful as a predictive adjuvant study for endometrial adenocarcinoma biopsy specimens.

Adenocarcinoma↗

Contribution of HER-2/neu oncogene expression to tumor grade and DNA content analysis in the prediction of prostatic carcinoma metastasis.

BACKGROUND: Recent advances in the early detection of prostatic adenocarcinoma have stimulated interest in the development of techniques for determining metastatic potential. METHODS: One hundred cases of adenocarcinoma, including 66 biopsy and radical prostatectomy specimens; 20 biopsies alone; and 14 transurethral resection specimens, were evaluated for Gleason tumor grade, DNA content and HER-2/neu expression. DNA content was determined on Feulgen-stained touch preparations and tissue sections (18 cases) or tissue sections alone. HER-2/neu expression level was determined by image-analysis-assisted quantitative immunocytochemistry. RESULTS: Tumor grade and ploidy status were independent significant predictors of metastasis. HER-2/neu overexpression was found in 16 (16%) of the 100 cases and significantly correlated with high-tumor grade and aneuploid status, but was not of independent value in the prediction of metastasis. CONCLUSIONS: HER-2/neu overexpression is not uncommon in prostatic adenocarcinoma and is associated with high-tumor grade, abnormal DNA content, and distant metastasis. Tumor grade and DNA ploidy values are of the greatest value in determining the presence of metastasis.

Adenocarcinoma↗

Correlation of tumor cytosol cathepsin D with differentiation and invasiveness of endometrial adenocarcinoma.

The lysosomal acidic protease cathepsin D, a recognized independent predictor of prognosis in human breast cancer, has not been studied widely in patients with endometrial adenocarcinoma. Cathepsin D levels (52-kD precursor plus 48-kD intermediate and 34/14-kD mature form) were measured in tumor cytosols from 26 hysterectomy specimens by immunoradiometric assay. Significant correlation between cathepsin D levels and tumor differentiation was noted with linear increase in cathepsin D from 8 pmol/mg (standard error of the mean [SEM], 1.73 pmol/mg) for Grade I tumors to 28 pmol/mg (SEM, 3.91 pmol/mg) for Grade III tumors. A group of four papillary serous carcinomas showed relatively high cathepsin D levels reaching 39 pmol/mg. A significant stepwise increase in cathepsin D levels was associated with increased depth of myometrial invasion. Noninvasive tumors averaged 7 pmol/mg (SEM, 4.0 pmol/mg); intramural tumors averaged 15 pmol/mg (SEM, 2.45 pmol/mg); and transmural invasive tumors averaged 30 pmol/mg (SEM, 3.72 pmol/mg). There was no significant correlation of cathepsin D levels with age, estrogen/progesterone receptor hormone status, clinical stage, and lymph node metastasis. Cathepsin D levels correlate significantly with tumor differentiation and myometrial invasiveness and may show promise as a clinically useful adjunct to prognosis assessment and the planning of therapy for patients with endometrial adenocarcinoma.

Adenocarcinoma↗

Prostatic carcinosarcoma: case report and review of literature.

True carcinosarcoma of the prostate is a rare neoplasm, with only 9 cases well documented by immunocytochemistry and ultrastructural examination. We report a case of an unresectable pelvic tumor studied at autopsy. The primary prostatic neoplasm and pulmonary metastases were composed of well differentiated adenocarcinoma admixed with foci of leiomyosarcoma and osteosarcoma. The sarcomatous components showed reactivity with vimentin and desmin, did not express prostatic acid phosphatase (PAP) and prostate specific antigen (PSA), and contained myofilaments on electron microscopic examination. Positive staining of the carcinomatous component for PAP and PSA was noted. These findings confirm the mixed epithelial and mesenchymal components in primary and metastatic sites, and support the diagnosis of true prostatic carcinosarcoma.

Adenocarcinoma↗

Histologically pure seminoma with elevated alpha-fetoprotein: a clinicopathologic study of ten cases.

Seminomas account for 50% of testicular germ-cell tumors, and more than 90% of these are classic seminomas. When patients with a histologically pure testicular seminoma show an elevated level of serum á-fetoprotein (AFP), it is generally assumed that an undetected focus of yolk sac tumor (YST) is present and the patient is managed with a treatment regimen for non-seminomatous tumor. We studied 10 cases of histologically pure seminoma with elevated levels of serum AFP in an attempt to identify any distinctive clinical, histopathologic, or immunohistochemical features. The patients ranged in age from 27 to 48 years (mean, 31 years). Eight patients had primary tumors of the testis, and two presented with supraclavicular and ileal tumors. The clinical stage at presentation varied: four tumors were stage I, four were stage II, and two were stage III. Serum levels of AFP were elevated in all patients at ranges of 10.4 to 16 ng/ml (mean, 12.0 ng/ml). In all patients, the primary tumors and metastases when present exhibited classic seminoma histology without other germ-cell components. The tumor cells expressed keratin in seven cases. The pattern of keratin immunoreactivity ranged from focal staining in five cases to moderate staining in two cases. All cases were negative for AFP, and the nine cases in which staining for CD30 (Ki-1) was performed were also negative. All four patients with stage I tumors underwent the conventional therapy for pure seminoma, i.e., orchiectomy and subsequent radiation therapy. Five patients received treatment for non-seminomatous tumors, i.e., chemotherapy after orchiectomy. Extensive work-up failed to detect the primary tumor in one patient, and he was treated for a non-seminomatous tumor, undergoing chemotherapy and irradiation. All patients are alive and well, and none has developed evidence of YST at a mean follow-up of 6 years (range, 6 months to 10 years). However, one patient who presented with an ileal metastasis recently developed a second primary extragonadal mediastinal mixed germ-cell tumor with YST and embryonal carcinoma components and an elevated serum level of AFP (27,000 ng/ml) after a 10-year disease-free follow-up. This study strongly suggests that minor elevations (</= 16 ng/ml) of AFP in patients with an otherwise pure seminoma may not indicate that there is a hidden focus of YST and that such patients should be treated with standard therapy for seminoma. Because this study includes very few patients, further studies are required to better understand the significance of borderline elevations of AFP in cases of histologically pure seminoma.

Adult↗