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H Salazar

Publications and source records attributed to H Salazar.

At least 19 recordsLinked to original sources
PubMed2000

Cadherin expression in glandular tumors of the cervix.

BACKGROUND: The cadherins are homotypic adhesion proteins that are important in cell sorting during organogenesis. Classic cadherins include several different types that show tissue specific expression. Specific tissue expression of cadherins often is preserved in neoplastic transformation, and cadherin phenotype can be used to differentiate morphologically similar but histogenetically distinct tumors. METHODS: The authors examined by using immunohistochemistry in paraffin sections the expression of E- (epithelial) and P- (placental) cadherin in 39 patients with glandular tumors of the cervix, including invasive adenocarcinoma, villoglandular adenocarcinoma, adenocarcinoma in situ (AIS), and adenoma malignum. RESULTS: In all cases, E-cadherin was expressed in both normal and malignant glands without appreciable differences. P-cadherin, normally confined to basal epithelial cells and not observed in benign glands, was aberrantly expressed in neoplastic glands in 27 cases, including 96%(23 of 24 cases) of invasive cancers, 40% (2 of 5) of villoglandular carcinomas, 25% (2 of 8) of AIS, and 0% (0 of 2) of adenoma malignum. CONCLUSIONS: The authors' results show that E-cadherin is uniformly expressed in glandular tumors of the cervix with no evidence of decreased expression in these tumors. In addition, P-cadherin is aberrantly expressed in most adenocarcinomas and appears to be preferentially expressed in invasive rather than in situ lesions. Thus, aberrant expression of P-cadherin may be a useful marker of invasive or aggressive clinical behavior in glandular lesions of the cervix.

Adenocarcinoma↗
PubMed2000

The International Society of Gynecological Pathologists. Its founding and early years.

The International Society of Gynecological Pathologists was founded in 1976 to facilitate an exchange of knowledge about gynecological disease throughout the world. The Society moved quickly to schedule companion meetings with established international and regional pathology and gynecology societies, including the International Academy of Pathology, its United States-Canadian Division, and the International Federation of Gynecology and Obstetrics, and to sponsor smaller meetings within individual countries. In 1981 the Society founded this journal, and in 1983, at the invitation of the World Health Organization, it assumed the responsibility of revising the WHO classifications of tumors of the female genital tract. The foundation of the Society appears to have been solid in view of its present robust health.

Female↗
PubMed2000

Nuclear localization of E-cadherin expression in Merkel cell carcinoma.

CONTEXT: Cadherins are cell-cell adhesion proteins that act as tumor suppressor genes and have a critical role in cell sorting and tissue formation during organogenesis. The pattern of cadherin expression constitutes a useful diagnostic and prognostic tool in the evaluation of tumors and for determining the histogenesis of tumor cells. We have previously characterized the cell types of several tumors based on the expression of individual cadherins. OBJECTIVE: To investigate the expression of cadherins in Merkel cell carcinomas. DESIGN: Paraffin immunohistochemical analysis of the 3 best-studied cadherins was performed on 35 cases of Merkel cell carcinoma. RESULTS: E-cadherin was expressed in 34 (97%) of 35 Merkel cell carcinomas examined, N-cadherin was expressed in 22 (63%) of 35 cases, and P-cadherin was expressed in 15 (43%) of 35 cases. This frequency of cadherin expression was similar to a group of small cell and neuroendocrine tumors from other primary sites. Interestingly, the localization of E-cadherin expression was unique in Merkel cell carcinomas compared with other primary neuroendocrine tumors. Merkel cell carcinomas showed marked preference for nuclear versus membrane localization, whereas small cell tumors from other sites showed fewer cases of nuclear E-cadherin expression. The nuclear localization of E-cadherin did not correlate with cadherin-associated protein beta-catenin nuclear expression. CONCLUSIONS: Our findings show that E-cadherin is the most frequently expressed cadherin in Merkel cell carcinoma, followed in frequency by N-cadherin then P-cadherin. The pattern of nuclear E-cadherin expression is more frequent for Merkel cell carcinoma than small cell tumors of other primary sites. These observations suggest that E-cadherin expression and function are altered in Merkel cell carcinoma, and this finding has potential use in the differential diagnosis of these tumors.

Breast Neoplasms↗
PubMed1999

P-cadherin expression in breast carcinoma indicates poor survival.

BACKGROUND: The cadherin family of cell-cell adhesion molecules and their associated proteins, the catenins, are essential to embryonic development and the maintenance of adult tissues. During development, the homotypic interaction of a particular cadherin with an identical cadherin expressed on a neighboring cell results in the sorting of cells to form distinctive tissues. Cadherins are believed to be tumor suppressors, and their altered expression and function have been associated with tumor development. METHODS: The authors examined the expression of P-cadherin, E-cadherin, and N-cadherin, and alpha-catenin and beta-catenin in 183 cases of invasive breast carcinoma by immunohistochemistry on paraffin sections using specific antibodies and a steam-based antigen retrieval method. RESULTS: P-cadherin was positive in 95 cases and negative in 88 cases of breast carcinoma. Positive P-cadherin expression in breast carcinoma showed a strong correlation with poor patient prognosis. Five years after surgery, 90% of the patients with P-cadherin negative tumors were alive in contrast to only 59% of patients with P-cadherin positive tumors. The difference in survival reached statistical significance (P = 0.0001) as early as 2 years after surgical treatment. Expression of N-cadherin, alpha-catenin, and beta-catenin did not correlate with patient survival. Multivariable statistical analyses of the data showed that expression of P-cadherin was independent of tumor size and lymph node metastases, but correlated inversely with estrogen/progesterone receptor status. In ductal carcinomas, positive P-cadherin expression correlated with a higher histologic grade. In contrast, expression of E-cadherin was low in high grade ductal carcinomas but negative tumors were uncommon. Negative or low E-cadherin expression did not correlate with poor survival. In lobular carcinomas, E-cadherin expression frequently was negative or low, and P-cadherin always was negative. CONCLUSIONS: Expression of P-cadherin in breast carcinoma is associated strongly with poor survival and constitutes an independent prognostic predictor. P-cadherin expression is a better indicator of clinical outcome than alterations in the expression of E-cadherin, N-cadherin, alpha-catenin, or beta-catenin.

Adult↗
PubMed1999

N-cadherin distinguishes pleural mesotheliomas from lung adenocarcinomas: a ThinPrep immunocytochemical study.

BACKGROUND: Cadherins are a family of cell-cell adhesion proteins. The homotypic binding of cadherins is critical for cell sorting and tissue formation during organogenesis. Different cadherin subtypes show lineage specific tissue expression, which has been exploited to differentiate histologically similar tumors of varying ontogeny. By applying immunohistochemistry to tissue sections, the authors have previously documented the utility of N-cadherin in distinguishing between pleural mesotheliomas and lung adenocarcinomas, based on the observation that N-cadherin is expressed in the former disease but not in the latter. Because the diagnosis of these diseases is frequently rendered on cytologic material rather than tissue biopsies, the authors wanted to assess the utility of N-cadherin immunocytochemistry in evaluating material prepared with ThinPrep. METHODS: The authors examined the cytologic material from 12 patients for the expression of N-cadherin using immunocytochemistry. Four patients had mesotheliomas and eight had adenocarcinomas. ThinPrep slides of the patients' pleural fluid were prepared and stained with the monoclonal antibody 13A9, which is specific for N-cadherin. RESULTS: Of the 12 cases studied, all 4 cases of pleural mesothelioma expressed N-cadherin in a specific cell-cell membrane location, and all 8 cases of lung adenocarcinoma were negative for N-cadherin. CONCLUSIONS: These results show that the N-cadherin specific antibody 13A9 is a suitable marker in material prepared with ThinPrep for the differentiation of pleural mesotheliomas from lung adenocarcinomas. This antibody should be included in the diagnostic immunocytochemical panel for evaluation of these malignancies.

Adenocarcinoma↗
PubMed1999

Distinct cadherin profiles in special variant carcinomas and other tumors of the breast.

The cadherins are homotypic adhesion proteins that are important in cell sorting during organogenesis. Classical cadherins include several different types that show tissue-specific expression. Cell lineage-specific expression of different cadherin subtypes can differentiate morphologically similar but histogenetically distinct tumors. We examined by immunohistochemistry in paraffin sections, the expression of E (epithelial), N- (neural), and P- (placental) cadherin in 36 unusual tumors of the breast (22 medullary carcinomas, 5 metaplastic carcinomas, 2 carcinosarcomas, 4 phyllodes tumors, and 3 periductal stromal tumors). All carcinomas stain with E-cadherin (22 of 22 medullary and 5 of 5 metaplastic). E-cadherin also stained the epithelial component but not the sarcomatous areas of 2 of 2 cases of carcinosarcomas. E-cadherin was not detected in the stromal tumors (phyllodes, periductal stromal tumor). N-cadherin was most frequently expressed in sarcomatoid metaplastic carcinomas (5 of 5), and variably in other tumors, including the sarcomatous area of carcinosarcoma (1 of 2), and 6 of 22 medullary carcinomas. P-cadherin was frequently identified in medullary carcinomas (20 of 22), in 5 of 5 metaplastic carcinomas, and in the proliferating stroma and benign epithelium of 3 of 3 periductal stromal, but not in phyllodes tumors (0 of 4). All sarcomatoid metaplastic carcinomas co-expressed all 3 classical cadherins. Our results show that these breast tumors have unique patterns of cadherin expression suggesting different histogenetic origin or lines of differentiation. The cadherin profiles in these tumors may be useful for classification and diagnosis.

Breast Neoplasms↗
PubMed1998

Adenocarcinoma arising in extragonadal endometriosis: an immunohistochemical study.

BACKGROUND: Malignant transformation is an infrequent but reported complication of endometriosis. Previous reports of these cases have been limited to clinicopathologic studies based on routine histologic examination of these tumors, whereas, to the authors' knowledge, characterization of these lesions based on immunophenotype and hormone receptor and oncoprotein expression has not been described. METHODS: Using commercially available monoclonal antibodies, the authors studied three recent cases of adenocarcinoma arising in extragonadal endometriosis using paraffin immunohistochemistry. Proteins examined included different cytokeratin (CK) subtypes, as well as hormone receptor status, proliferation rate, and oncoprotein expression. RESULTS: All three cases presented clinically and macroscopically as colonic masses, and the tumors expressed an endometrial CK phenotype (CK7+, CK20-). In contrast, the adjacent benign colonic epithelium expressed the expected opposite phenotype (CK7-, CK20+). Estrogen receptor (ER) and progesterone receptor (PR) were expressed in one of the three tumors. Interestingly, in the ER/PR negative tumors, receptor expression was present in areas of benign endometriosis adjacent to malignancy, suggesting a loss of receptor expression with malignant transformation. The tumors also were examined for proliferation by Ki-67, and the expression of oncoproteins c-erb B-2, p53, cyclin D1, and bcl-2. All cases of malignancy had a high proliferation rate as measured by Ki-67, which was in contrast to areas of benign endometriosis which had a low proliferation rate. Of the other oncoproteins only p53 protein was detected at a significant level in all three cases. Cyclin D1 was overexpressed in two of the three cases. c-erb B2 and bcl-2 overexpression was not detected. CONCLUSIONS: The results of the current study 1) show the utility of CK subtypes in confirming endometrioid phenotype in tumors arising in extragonadal endometriosis with colonic involvement and 2) suggest that loss of hormone receptor expression and p53 oncoprotein abnormalities may be involved as mechanisms in malignant transformation in extragonadal endometriosis.

Abdominal Muscles↗
PubMed1997

Immunohistochemical analysis of beta-tubulin isotypes in human prostate carcinoma and benign prostatic hypertrophy.

BACKGROUND: beta-tubulin, the intracellular target of several antimicrotubule agents, is encoded by at least six genes and exists as multiple isotypes with tissue-specific expression. Previous in vitro studies indicated that tubulin isotype composition may affect polymerization properties, dynamics, and sensitivity to drugs. METHODS: To investigate the isotype composition of beta-tubulin in human prostate, tissues were collected from 26 patients after radical prostatectomy and sections were stained with isotype-specific antibodies. RESULTS: beta IV tubulin is the predominant isotype in benign prostatic hyperplasia (BPH) and adenocarcinoma, showing significantly stronger immunohistochemical expression than beta II and beta III, particularly in Gleason's grade 3 and 4 cancers. Staining for the beta II isotype was invariably weak and often absent in BPH and normal glands. There was a marked increase in beta II isotype stain from BPH to cancer in 77% of the patients, suggesting that the expression of this isotype is related to malignant status. CONCLUSIONS: The beta II tubulin isotype is a potential marker for prostate adenocarcinoma. The possibility that tumor beta-tubulin isotype composition may effect the response to antimicrotubule drug therapy in prostate cancer and other tumors merit investigation.

Carcinoma↗
PubMed1997

Differential expression of N-cadherin in pleural mesotheliomas and E-cadherin in lung adenocarcinomas in formalin-fixed, paraffin-embedded tissues.

The differential diagnosis of pleural mesotheliomas and lung adenocarcinomas presents a continued challenge in the practice of surgical pathology. Paraffin immunohistochemistry (IHC) using different panels of antibodies can be helpful in some cases, but, as yet, no antigen is expressed specifically in mesotheliomas nor in adenocarcinomas. Using well characterized monoclonal antibodies (MAb) that recognized distinct mesenchymal and epithelial adhesion proteins, N-cadherin (13A9 MAb) and E-cadherin (E9 MAb), respectively, we found previously that in frozen-section IHC mesotheliomas and adenocarcinomas had distinct cadherin phenotypes: mesotheliomas were positive for N-cadherin, and lung adenocarcinomas were positive for E-cadherin. Using antigen-retrieval methods, we successfully extended our study to formalin-fixed, paraffin-embedded tissue sections. Tumors from 28 patients (14 originally diagnosed as mesotheliomas, and 14 diagnosed as adenocarcinomas) were stained with 13A9 MAb and E9 MAb. Review of hematoxylin-eosin sections excluded from analysis one case previously diagnosed as mesothelioma, which represented a hemangiopericytoma. Of the remaining 27 cases, 12 of 13 mesotheliomas were positive for N-cadherin and negative for E-cadherin. The exception was a multifocal microscopic papillary tumor of apparent mesothelial origin, which was negative for both N-cadherin and E-cadherin. Conversely, 13 of 14 adenocarcinomas were E-cadherin positive and N-cadherin negative except for one adenocarcinoma with focal N-cadherin expression. One case of a poorly differentiated adenocarcinoma invading skeletal muscle was negative for both 13A9 and E9. These studies confirmed the utility of the cadherin antibodies in distinguishing pleural mesotheliomas from lung adenocarcinomas. The reactivity of the cadherin-specific antibodies with antigens in paraffin sections make them powerful and reliable markers in the practice of diagnostic surgical pathology.

Adenocarcinoma↗
PubMed1997

Expression of E-cadherin and N-cadherin in surface epithelial-stromal tumors of the ovary distinguishes mucinous from serous and endometrioid tumors.

This study examines the expression of E-cadherin and N-cadherin in the most common epithelial tumors of the ovary. The homotypic interactions of distinctive members of the cadherin family of cell-cell adhesion molecules segregate cells into tissues during embryonic development, and their expression in tumors can be used to trace the histogenesis of tumor cells. Because the surface epithelium of the ovary is a modified mesothelium, we speculated that the expression of E (epithelial)-cadherin and N (neural, mesodermal)-cadherin may provide clues about the controversial origin of common epithelial ovarian tumors. Immunohistochemistry was performed in paraffin sections using well-characterized monoclonal antibodies to E- and N-cadherin and heat-induced antigen-retrieval methods. We found that serous and endometrioid tumors express both E- and N-cadherin. In contrast, mucinous tumors strongly express E-cadherin, but no N-cadherin. The presence of N-cadherin in serous and endometrioid tumors traces their origin to the mesoderm-derived ovarian surface epithelium. The absence of N-cadherin in mucinous tumors clearly distinguishes them from the former, suggesting histogenesis from a cell lineage other than the ovarian surface epithelium or aberrant differentiation mechanisms associated with neoplastic transformation.

Biomarkers↗
PubMed1997

[Late reopening of patent ductus arteriosus after complete closure with the Rashkind prosthesis. Possible traumatic origin].

We report the case of a symptomatic adult with an occluded persistent duct with a transcatheter proceeding using a Rashkind prosthesis. After a month of follow up the color-coded Doppler-flow echocardiogram did not show residual shunt, posteriorly the patient's symptoms disappeared and the left ventricular dimensions were reduced. At the thirteen month of follow-up, the patient had an accident while working, falling down from a scaffold. Afterwards, a ductal jet was observed in the echocardiogram with an increased size of the left ventricle, symptoms also appeared. A cardiac catheterism was then performed showing a pulmonary/systemic flow rate of 2 and a 3 mm flow jet at the superior border of the prosthesis. A second prosthesis was implanted with no residual shunts.

Accidental Falls↗
PubMed1997

Expression of P-cadherin identifies prostate-specific-antigen-negative cells in epithelial tissues of male sexual accessory organs and in prostatic carcinomas. Implications for prostate cancer biology.

Cadherins constitute a family of calcium-dependent cell-cell adhesion molecules the individual members of which are essential for the sorting of cells into tissues during development. In this study, we examined the expression of E-cadherin, N-cadherin, and P-cadherin in tissues obtained from radical prostatectomies. Epithelial cells of prostatic glands, ejaculatory ducts, and seminal vesicles expressed E-cadherin but not N-cadherin. P-cadherin was expressed in epithelial cells of the seminal vesicles and ejaculatory ducts. In the prostate it was limited to the basal cells of prostatic acini, glands with basal cell hyperplasia, and atrophic glands denuded of the luminal cells. All P-cadherin-positive cells were negative for prostatic-specific antigen. Prostatic cancers were mostly P-cadherin negative, but some tumors had P-cadherin-positive areas frequently located close to ejaculatory ducts and negative for prostatic-specific antigen. The mutually exclusive expression of P-cadherin and prostatic-specific antigen suggests that these proteins are involved in differential mechanisms of cell regulation in prostate cancer. P-cadherin may become a useful marker in the diagnosis and management of patients with prostate cancer and low levels of prostatic-specific antigen.

Animals↗
PubMed1996

Microscopic benign and invasive malignant neoplasms and a cancer-prone phenotype in prophylactic oophorectomies.

BACKGROUND: The occurrence of approximately 5% of common epithelial malignant tumors of the ovary can be traced to inheritance of risk. One prophylactic strategy to decrease the probability of development of disease in individuals within families where this mendelian-dominant pattern of occurrence is apparent is to remove the ovaries of individuals at risk for ovarian cancer. The procedure, when done for this purpose, is recommended soon after completion of childbearing. PURPOSE: Our goal was to compare the histologic features of the ovaries of women at increased risk for ovarian cancer to those at no known increased risk for the disease. METHODS: Ovaries removed for prophylaxis from 20 women considered to be at increased risk for developing ovarian cancer were examined histologically. During the course of this work, it seemed apparent that these ovaries contained numerous atypical features compared with the expected appearance of normal ovaries. Hence, we expanded the study to include a control group whose ovaries were removed for reasons unrelated to cancer. The study, therefore, was not blinded. The increased risk in the cancer-prone individuals was determined by family history, specifically the presence of at least one first-degree relative and one second-degree relative with ovarian and/or breast cancer and positive linkage or mutational analysis of BRCA1 in some. The difference in mean ages of patients in the control and high-risk groups was not statistically significant. The difference among both groups with respect to the number of atypical features as well as the intensity of those features was ascertained by computing probabilities using Fisher's exact test (two-sided) for rows x columns contingency tables. RESULTS: Two unanticipated microscopic or near-microscopic malignant neoplasms and other benign and borderline tumors were discovered in the ovaries of the high-risk individuals. Of substantial interest was the finding that among the ovaries of high-risk women, 85% presented two or more and 75% presented three or more of the following histologic features: surface epithelial pseudostratification; surface papillomatosis; deep cortical invaginations of the surface epithelium, frequently with multiple papillary projections within small cystic spaces (microscopic papillary cystadenomas); epithelial inclusion cysts, frequently with epithelial hyperplasia and papillary formations; cortical stromal hyperplasia and hyperthecosis; increased follicular activity; corpus luteum hyperplasia; or hilar cell hyperplasia. Two or more or three or more such changes were observed in a lesser percentage (30% or 10%, respectively) of ovaries obtained from the control individuals, with a statistically significant difference (P = .001 or P = .00007, respectively), particularly considering that a detailed determination of a family history of cancer in the control group was not possible. CONCLUSIONS: The frequency of these changes in the high-risk ovaries compared with control ovaries suggests a characteristic histologic preneoplastic phenotype defined by an increased frequency and intensity of the above-described histologic features in the high-risk ovaries. Limited access to numerous small (stage I) ovarian cancers or cancer-prone ovaries by any one pathologist may explain the failure to identify the phenotype in the past. IMPLICATIONS: We suggest that the ovaries removed from ovarian cancer-prone individuals as a preventative measure should be thoroughly examined histologically to identify or rule out microscopic or near-microscopic invasive neoplasms.

Adult↗
PubMed1996

Preoperative chemoradiotherapy for localized pancreatic carcinoma. A perspective.

BACKGROUND: The role of chemotherapy (CTX) in the treatment of localized adenocarcinoma of the pancreas must be enhanced if current results are to be surpassed. It is postulated that histologic response to various chemotherapeutic agents may offer an assessable endpoint intermediate to and perhaps as or more meaningful than survival analysis. METHODS: A history of trials assessing the value of adjuvant preoperative and postoperative chemotherapy and radiation therapy (RT) is provided. Experiences with histologic assessment of treatment response are reviewed. RESULTS: There has been no clear benefit from adjuvant CTX, either when delivered with RT or as postoperative maintenance. Imaging tests were much less sensitive than histologic grading in determining responses (7% vs. 71% partial responses) of patients with resected pancreatic cancers previously treated with RT/CTX. This suggests that standard imaging assessments of pancreatic carcinoma response to chemotherapy and radiation therapy may be inaccurate. CONCLUSIONS: Preresectional delivery of chemotherapeutic agents with RT allows response rates to be quantified histologically. This method of response analysis, being much more sensitive than analysis by computed tomographic scanning, may allow the more rapid development of improved chemotherapeutic programs for this malignancy.

Adenocarcinoma↗
PubMed1996

Loss of heterozygosity studies indicate that chromosome arm 1p harbors a tumor supressor gene for renal oncocytomas.

We carried out a complete genome scan for loss of heterozygosity (LOH) in four renal oncocytomas by using highly polymorphic CA repeat microsatellite loci. Three of the four tumors exhibited LOH for chromosome arm 1p, and the oncocytomas of both female patients lost Xq. Therefore, these chromosome arms may harbor tumor suppressor genes involved in the etiology of this disease. Although the genomes of ontocytomas are relatively stable, two different microsatellite loci in one tumor were mutated by + or - 2 nt. Similar alterations in CA repeats that are probably due to spontaneous mutation have been observed in renal cell carcinomas.

Adenoma, Oxyphilic↗
PubMed1995

Genomic alterations and instabilities in renal cell carcinomas and their relationship to tumor pathology.

A comprehensive genome scan for loss of heterozygosity (LOH) in 33 renal cell carcinomas indicates that mutations of tumor suppressor genes on several different chromosomes are required for malignant transformation in this disease. In the case of nonpapillary renal carcinomas chromosomes 3p, 6q, 8p, 9pq, and 14q exhibit elevated levels of LOH. Although 3p is the most frequently lost chromosome arm, in no case is 3p observed as the sole allelic loss because it always occurs in conjunction with the loss of either 6q, 8p, or 14q. This result indicates that the mutation of a tumor suppressor gene on 3p, most likely von Hippel-Lindau disease (VHL), may be necessary but is not sufficient for the development of nonpapillary renal cell carcinoma. In papillary renal tumors, LOH is observed most often for chromosomes 6pq, 9p, 11q, 14q, and 21q. This suggests that tumor suppressor genes located on chromosomes 6q, 9pq, and 14q may be involved in the development and/or progression of both nonpapillary and papillary renal cell carcinomas. However, LOH in papillary tumors appears to be especially elevated for 11q and 21q and reduced for 3p and 8p indicating that there are also tumor suppressor genes specific to each form of the disease. There is no correlation between stage of disease and the extent of LOH, loss of a particular chromosome, or the number of chromosomes that show allele imbalance. Early and late stage tumors may exhibit either extensive LOH or no apparent allele loss; similarly, allelic imbalances are observed in both early and late stage renal cell carcinomas. This suggests that a gene (or genes) regulating mitotic chromosome stability may be mutated in some renal tumors. Preliminary evidence points to an association between genome instability and LOH of 14q. Finally, a distinct type of microsatellite instability has been detected in 21% of renal cell carcinomas and occurs at a frequency of 4.4 x 10(-4)/locus. The most common mutation is a 2-bp insertion in a CA repeat. This alteration is not restricted to a particular histopathology or clinical stage, and it is not associated with allelic loss of a specific chromosome. The frequency of this event is similar to that which occurs spontaneously in germline microsatellite loci and is probably not the result of a defect in a mismatch repair gene. It is possible that this type of microsatellite instability is general and may occur in most, if not all, carcinomas.

Alleles↗
PubMed1995

Comprehensive allelotyping of human renal cell carcinomas using microsatellite DNA probes.

The von Hippel-Lindau locus on chromosome 3p is a tumor suppressor gene known to be involved in nonpapillary renal cell carcinoma. A previous loss of heterozygosity (LOH) study aimed at determining the allelotype of kidney tumors has indicated that in addition to 3p, chromosome arms 5q, 6q, 10q, 11q, 17p, and 19p may also harbor tumor suppressor genes. However, cytogenetic studies reveal that chromosomes 3p, 6q, 8p, 9pq, and 14q most frequently undergo karyotypic changes in renal tumors. To resolve these differences, a collection of microsatellite DNA probes has been used to scan for LOH so that 90% of individual tumor genomes were rendered informative for allele loss. The assay is capable of detecting quantitative genomic alterations in tumor cells as well. We find that LOH is most frequent for chromosome arm 3p. However, in no tumor is 3p exclusively affected. LOH for 6q, 8p, 9pq, and 14q is also distinctly elevated for both nonpapillary as well as papillary tumors and suggest that many of the tumor suppressor loci involved may be common to the etiology of both forms of kidney cancer.

Alleles↗