Matrix metalloproteinases-2, -3, and -9 secreted by explants of benign and malignant lesions of the uterine cervix.

Elevated expression of matrix metalloproteinases (MMPs) plays a critical role in extracellular matrix (EM) degradation in tumor development and prognosis of different human carcinomas. In cervical carcinoma (Ce Ca), the role of these proteinases in the biological development of this neoplasm is controversial. In the present study, we compared the secretion of MMP-2, MMP-3 and MMP-9 among 29 benign and premalignant cervical lesions (cervicitis and cervical intraepithelial neoplasias) and 46 tumoral explants of Ce Ca. The explants were cultured for 48 h. The gelatinases secreted into conditioned medium were revealed by zymography and quantified by densitometry. The results showed high levels of MMP-3 and MMP-9 in tumoral explants. In contrast, only the pro-MMP-2 was higher in benign cervical lesions, although both active and inactive MMP-2 species are associated with advanced clinical stages in tumoral samples, and only the secretion of MMP-3 was associated with unresponsiveness to radiotherapy. We can conclude that the expression of MMPs is related to the invasive process in Ce Ca and suggest that they may play a role in degradation of the EM during local invasion. In addition, MMP-3 secretion could be a marker of poor prognosis in Ce Ca.

Membrane proteins in neoplasic and normal uterine cervix.

Tumor cells exhibit phenotypic and genotypic differences in comparison to normal cells. These differences can be used to identify proteins important for tumor growth and, therefore, potentially used in the diagnosis and follow-up of patients. The objective of this work was to investigate the electrophoretic pattern of cytoplasm membrane proteins from normal and malignant cervix using polyacrylamide-SDS gels. A highly reproducible protein pattern was found in the 29 samples of normal cervix whereas three well-defined patterns of protein bands were observed in the 48 tumor specimens (pattern I: 25%, pattern II: 29.2% and pattern III: 45.8%). A low concentration or absence of high molecular weight proteins was observed (p<0.5) in tumor samples. None of the tumor protein patterns correlated with the clinicopathologic characteristics of patients. Nine out of 11 patients (82%) showing the pattern III had a complete clinical response whereas only 55% (11 out of 20) of those with patterns I and II showed a complete response. However, this difference was non-significant (p=0.1247). In conclusion, we demonstrate that there is a gain and loss of cytoplasmic membrane proteins in tumors, shown as different protein band patterns. These findings could have clinical and biological significance that must be further evaluated.

Matrix metalloproteinases expressed in squamous cell carcinoma of the oral cavity: correlation with clinicopathologic features and neo-adjuvant chemotherapy response.

Secretion of gelatinases A (MMP-2) and B (MMP-9) from 21 tumoral explants of squamous cell carcinoma (SCC) and five samples of normal mucosa of the oral cavity is demonstrated here. The explants were cultured into fetal bovine serum- and phenol red-deprived medium for 48 hours. The gelatinases secreted into the medium were revealed and quantified by zymography and densitometry, respectively. The results showed high medians of the 66 kDa forms of gelatinase A in tumoral explants, in comparison to normal explants: 31.0 vs 5.9 densitometric units (DU) (p <0.01). There was also a relatioship between clinical response to neo-adjuvant chemotherapy and low activity of 66 kDa form of gelatinase A, as well as 84 kDa and 92 kDa forms of gelatinase B. The median of gelatinolysis of the inactive form of gelatinase A (72 kDa form) was higher in those patients who exhibited a complete response to neo-adjuvant chemotherapy. We conclude that gelatinase A is a useful and objective tool to evaluate the response to chemotherapy and the aggressiveness of carcinomas of the oral cavity.

[Expression of cathepsin D in breast cancer and its clinical and histopathological correlations]. / Expresión de catepsina D en carcinoma mamario y sus correlaciones clínicas e histopatológicas.

BACKGROUND: Cathepsin D is a lysosomal protease which is overexpressed in some cases of breast cancer. Several studies done in tumor cytosol have shown that high levels of cathepsin D are associated with poor prognosis in patients with breast cancer but the results are not conclusive using immunohistochemistry methods to assay cathepsin D. OBJECTIVE: To evaluate if cathepsin D, assayed by a immunohistochemical technique using a polyclonal antibody, can be considered an independent prognostic factor in breast cancer. PATIENTS AND METHODS: Paraffine embedded sections of 68 tumor specimens from breast cancer patients in stages I to IV seen at the Instituto Nacional de Cancerologia during the period from 1985 to 1986. RESULTS: From the 68 patients, 35 (51%) had an intense positive staining for cathepsin D, 19 (28%) han mild staining and 14 (21%) were negative. Ten patients with mild staining had artifacts due to deficiencies in the tissue fixation technique. Cathepsin D expression did not have a prognostic value nor association with other clinical and histopathological prognostic factors well established in breast cancer. CONCLUSION: Cathepsin D determined by immunohistochemistry has no prognostic value in breast cancer.

Peripheral neuroectodermal tumor of the chest wall in a patient treated for Hodgkin's disease.

The occurrence of second malignancies after treatment for Hodgkin's disease is a well recognized phenomenon. In this report we describe a case of a 22-year-old male who developed a peripheral neuroectodermal tumor of the chest wall four years after completing successful treatment with combined chemotherapy and radiotherapy for Hodgkin's disease.

Histopathologic changes of the nasal mucosa in southwest Metropolitan Mexico City inhabitants.

Metropolitan Mexico City (MMC) is one of the most polluted urban areas in the world. The authors characterized the morphologic nasal mucosal changes in short-term (less than 30 days) and long-term (more than 60 days) exposures to the polluted southwest MMC atmosphere with high levels of ozone and other contaminants versus a control group of subjects living in a nonpolluted, low-ozone Mexican port. Seventy-six inferior turbinate biopsies were examined. The control group showed normal mucociliary epithelium, whereas the short-exposure group displayed loss of normal epithelium, basal cell hyperplasia, and mild dysplasia (17.64%). In the long-term exposure group, 78.72% of dysplasias were found (59.45% mild and 40.54% moderate) together with severe loss of normal respiratory epithelium, prominent basal cell hyperplasia, squamous metaplasia, and submucosal vascular proliferation. Our findings suggest that southwest metropolitan Mexico City inhabitants develop histopathologic changes in their nasal mucosa on exposure to the polluted city atmosphere.

Oxyphil and squamous variants of medullary thyroid carcinoma.

Two unusual morphologic variants of medullary thyroid carcinoma not previously described are reported. The first tumor was composed predominantly of large eosinophilic cells indistinguishable at the light microscopic level from Hürthle cells. Focal areas of conventional medullary carcinoma were also present. Electron microscopic study showed mitochondrion-rich cells containing round neurosecretory granules. Immunoreactive calcitonin and carcinoembryonic antigen (CEA) were demonstrated within most tumor cells. The second tumor had areas of typical medullary carcinoma but exhibited extensive squamous differentiation. The tumor was positive for CEA, neuron-specific enolase, and chromogranin but negative for calcitonin. Oxyphil and squamous cells must be added to the long list of cell types that have been described in medullary thyroid carcinoma.