Carcinoma Histological Subtype Research Articles

C-met proto-oncogene expression in benign and malignant human renal tissues.

Hepatocyte growth factor/scatter factor (HGF/SF) is a potent mitogen to renal epithelial cells in vitro and in vivo. HGF/SF signals through its receptor which is coded by the c-met proto-oncogene. We hypothesized that altered expression of the HGF/SF receptor, c-met, may be involved in the pathogenesis of certain renal cell carcinomas. Our objectives were to 1) assess the presence and localization of c-met protein in benign and malignant human renal tissues, and 2) correlate the presence of c-met protein with renal carcinoma histological subtype, tumor stage and tumor grade. Immunohistochemical analysis of c-met protein was performed in 41 normal and malignant human renal samples. c-met Immunostaining was detected in the normal kidney tissue in all 41 samples. In the normal kidney c-met immunostaining was limited to the cell membrane and/or cytoplasm of epithelial cells in specific tubular segments, including the proximal convoluted tubule, thin and thick limbs of the loop of Henle, and the collecting duct. The glomeruli, distal convoluted tubule and stroma were consistently negative for c-met staining. c-met Immunostaining was detected in 68% of renal cell carcinomas and was more common in higher nuclear grade cancers (p < 0.034). The c-met receptor is present in specific tubular segments in the normal kidney and is frequently expressed in higher nuclear grade renal cancers, suggesting a role in renal carcinoma progression. Future studies should evaluate the biological significance of the HGF/ SF-c-met pathway in normal renal physiology, and renal cancer growth and progression.

C-Met Proto-Oncogene Expression in Benign and Malignant Human Renal Tissues

Purpose Hepatocyte growth factor/scatter factor (HGF/SF) is a potent mitogen to renal epithelial cells in vitro and in vivo. HGF/SF signals through its receptor which is coded by the c-met proto-oncogene. We hypothesized that altered expression of the HGF/SF receptor, c-met, may be involved in the pathogenesis of certain renal cell carcinomas. Our objectives were to 1) assess the presence and localization of c-met protein in benign and malignant human renal tissues, and 2) correlate the presence of c-met protein with renal carcinoma histological subtype, tumor stage and tumor grade. Materials and Methods Immunohistochemical analysis of c-met protein was performed in 41 normal and malignant human renal samples. Results c-met Immunostaining was detected in the normal kidney tissue in all 41 samples. In the normal kidney c-met immunostaining was limited to the cell membrane and/or cytoplasm of epithelial cells in specific tubular segments, including the proximal convoluted tubule, thin and thick limbs of the loop of Henle, and the collecting duct. The glomeruli, distal convoluted tubule and stroma were consistently negative for c-met staining. c-met Immunostaining was detected in 68% of renal cell carcinomas and was more common in higher nuclear grade cancers (p <0.034). Conclusions The c-met receptor is present in specific tubular segments in the normal kidney and is frequently expressed in higher nuclear grade renal cancers, suggesting a role in renal carcinoma progression. Future studies should evaluate the biological significance of the HGF/SF-c-met pathway in normal renal physiology, and renal cancer growth and progression.

Mutated K- ras gene analysis in a randomized trial of preoperative chemotherapy plus surgery versus surgery in Stage IIIA non-small cell lung cancer

The observation that the proteins encoded by ras genes play a central role in the signalling pathways used by cells to respond to growth factors and the fact that mutated ras proteins are constantly promoting cell division have led to a PCR-based hunt for additional clinical information. In the present study, K- ras analysis draws the following conclusions: (1) K- ras point mutation frequency was higher in the surgery group (10 of 24 patients) than in the chemotherapy-surgery group (3 of 20 patients). (2) Mutated K- ras was predominantly observed at codon 12 but five mutations appeared at codon 61. (3) Mutations were identified in the squamous cell carcinoma histological NSCLC subtype except in four cases corresponding to adenocarcinoma. (4) A multifarious pattern of substitutions, especially at codon 12, were noted with aspartic K 12 substitutions more prone to develop bone metastases. (5) Although a genotypic K- ras classification of NSCLC may not yet be formulated, our accumulated data (unpublished) suggest a trend toward it. (6) Patients with mutated K- ras tumors in the surgery group had no different survival than those with normal K- ras. However our pooled data as well as other authors' results assert that mutated K- ras constitute an additional prognostic datum that deserves to be included together with TNM classification. In the design of new preoperative (neoadjuvant) chemotherapy trials, stratification of tumors by K- ras status deserves to be further investigated in order to correlate with response, relapse and survival. Mutated K- ras genotype merits further research. Finally, the paradigm of uneven histological distribution and mutated K- ras spectra among researchers should serve as a stimulus to search for further contributions in this field.

Mammographic appearance of calcifications as a predictor of intraductal carcinoma histologic subtype

We reviewed 109 consecutive cases of intraductal carcinoma to evaluate the association between histologic subtype (comedo = 35, non-comedo = 71, mixed = 3) and calcification type, as assessed by histology (amorphous vs. crystalline) or by mammography (coarsely granular, irregular shape, linear, branching vs. fine granular, irregular, or more or less regular oval or circular forms). Calcifications were microscopically or mammographically detected in 90.8% and 76.1% of cases, respectively, and a significant association was found between microscopic (amorphous) and mammographic (coarse granular, linear, branching) calcified types and histologic comedo subtypes (P <0.001). Nevertheless, accurate prediction of the histologic subtype on the basis of mammographic calcifications occurred only in 78.3% of cases with calcifications, and in 59.6% of all cases. Mammography is not a reliable method to predict DCIS histologic subtype at the present time.

Relationship of CA 125 and CA 19.9 with lung carcinoma histological subtype: Preliminary study : Molina R, Santabarbara P, Filella X, Mengual P, Ballesta AM, Balague A. The University of Texas, Health Science Center at San Antonio, Dept. Medicine/Oncology, 7703 Floyd Curl Drive, San Antonio, TX 78284. Int J Biol Markers 1989;4:215–220

The aim of this work was to study the possible utility of simultaneous determination of CA 125 and CA 19.9 in patients with lung cancer. Serum levels of both markers were studied in 87 patients without metastases (Mo), 72 patients with distant metastases (MT) and 15 cases without clinical evidence of disease after primary treatment (NED). Sixty-five tumors were epidermoid, 34 were adenocarcinomas, 24 were cell undifferentiated carcinomas and 51 were small-cell carcinomas. Sera from 75 healthy subjects and 20 patients with benign lung disease were used as controls. The cut-off values used were 35 and 37 U/ml for CA 125 and CA 19.9, respectively. CA 125 and CA 19.9 serum levels were within normal limits in all control patients. In NED patients these markers were not elevated, except in one with chronic liver disease who showed elevated CA 19.9 (76 U/ml). Twenty-five percent of Mo lung cancer patients and 40.3% of MT cases had CA 19.9 over 37 U/ml. Abnormally high levels of CA 125 were found in 18.7% and 22.9% of Mo and MT patients, respectively. Sixty percent of patients with large cell undifferentiated carcinoma had elevated CA 125 (mean 176 U/ml) compared to 15.4% of patients with all other histological types of tumors combined (54.3 U/ml, p less than 0.01). CA 19.9 serum levels were also more often elevated in patients with large cell undifferentiated carcinomas (50%, 7/14 cases) than in other histological types (30%, 36/120 patients), but the difference was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship of CA 125 and CA 19.9 with lung carcinoma histological subtype: Preliminary study

The aim of this work was to study the possible utility of simultaneous determination of CA 125 and CA 19.9 in patients with lung cancer. Serum levels of both markers were studied in 87 patients without metastases (Mo), 72 patients with distant metastases (MT) and 15 cases without clinical evidence of disease after primary treatment (NED). Sixty-five tumors were epidermoid, 34 were adenocarcinomas, 24 were cell undifferentiated carcinomas and 51 were small-cell carcinomas. Sera from 75 healthy subjects and 20 patients with benign lung disease were used as controls. The cut-off values used were 35 and 37 U/ml for CA 125 and CA 19.9, respectively. CA 125 and CA 19.9 serum levels were within normal limits in all control patients. In NED patients these markers were not elevated, except in one with chronic liver disease who showed elevated CA 19.9 (76 U/ml). Twenty-five percent of Mo lung cancer patients and 40.3% of MT cases had CA 19.9 over 37 U/ml. Abnormally high levels of CA 125 were found in 18.7% and 22.9% of Mo and MT patients, respectively. Sixty percent of patients with large cell undifferentiated carcinoma had elevated CA 125 (mean 176 U/ml) compared to 15.4% of patients with all other histological types of tumors combined (54.3 U/ml, p less than 0.01). CA 19.9 serum levels were also more often elevated in patients with large cell undifferentiated carcinomas (50%, 7/14 cases) than in other histological types (30%, 36/120 patients), but the difference was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)