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M J Merino

Publications and source records attributed to M J Merino.

At least 73 records · Page 4Linked to original sources
PubMed1996

Advanced stage transitional cell carcinoma of the ovary.

Primary transitional cell carcinoma (TCC) of the ovary has been recently recognized as a separate subtype of epithelial cancer. It has been proposed that recognition of such tumors is important on clinical grounds because of a favorable response to chemotherapy and an improved patient survival. The authors reviewed the histological and clinicopathologic findings of 58 patients with advanced stage (stages III and IV) ovarian cancer with a view to determining the frequency of TCC and confirming the favorable prognosis. Of these cases, 15 (26%) were reclassified as TCC; 13 were predominantly TCC, and 2 had a mixed pattern with approximately 50% of the tumor being TCC. TCC patients ranged in age from 44 to 70 years of age (mean, 57). Ten of the patients had stage III disease, and five were stage IV. The tumor was unilateral in 2 cases and bilateral in 11 (2 unknown). Tumor size varied between 3 and 23 cm. Of the stage III patients, five were optimally debulked, and five had residual disease. All patients received the same type of chemotherapy. The median overall survival was 28 months. There was no significant difference in the clinical outcome of patients with TCC compared with that of patients with serous carcinomas. These data suggest that TCC does not confer a favorable prognosis or better response rate to chemotherapy.

Adolescent↗
PubMed1996

Genetic analysis of synchronous mucinous tumors of the ovary and appendix.

The coexistence of mucinous ovarian and appendiceal tumors in association with pseudomyxoma peritonei (PP) is well established. However, it has not been determined whether they represent independent or metastatic neoplasms. The authors analyzed microsatellites on chromosome 17q 21.3-22 (nm23), 3p 25-26 (von Hippel Lindau disease [VHL] gene), and 5q 21-22 (D5S346 locus) in 12 synchronous ovarian and appendiceal mucinous lesions. Loss of heterozygosity (LOH) at the nm23 locus has been shown previously in ovarian carcinomas, and genetic alterations at both the 3p and 5q loci have been reported in colorectal carcinomas. The ovarian lesions consisted of nine mucinous tumors of low malignant potential and three invasive adenocarcinomas, and the appendiceal lesions consisted of eight carcinomas without invasion, two invasive carcinomas, and two mucosal hyperplasias. DNA was extracted from microdissected cells obtained from formalin-fixed, paraffin-embedded tissue sections and amplified by polymerase chain reaction. In three specimens, genetic alterations occurred at 17q 21.3-22 in only the ovarian tumors. One of these cases showed LOH on chromosome 5q 21-22 in only the appendiceal tumor. In three other specimens, LOH at the same locus was found in both tumors. Six specimens did not show LOH at any locus. These results suggest that a subset of synchronous mucinos ovarian and appendiceal lesions showing different LOH patterns in both sites most likely represent patients with two separate primary lesions. Another group of specimens with the same allelic loss in both tumors most likely represent patients with a single primary and metastatic spread. Thus, genetic analysis of these lesions may be useful in investigating the origin of histologically similar synchronous tumors.

Adenocarcinoma, Mucinous↗
PubMed1996

LOH at the APC/MCC gene (5Q21) in gastric cancer and preneoplastic lesions. Prognostic implications.

The APC/MCC gene (Familial Adenomatous Polyposis) at 5q21 plays a role in colon cancer carcinogenesis. LOH at this locus has also been described in gastric cancer and preneoplastic lesions. The APC locus has been recently related to a cell surface adhesion molecule and its alteration may favour metastatic dissemination. LOH at 5q21 has been associated with poor prognosis in other tumors such as lung cancer. Thirty-six gastric cancers were evaluated for LOH at 5q21 with 2 polymorphic markers from microdissected paraffin-embedded material. All tumors were classified by stage, histologic type, degree of differentiation and survival rates. In 4 cases, intestinal metaplasia cells in the adjacent mucosae were also microdissected. Six cases of moderate-severe gastric dysplasia were also added to the study. LOH was determined in 84% of the informative cases of GC, affecting both early and advanced stages of disease. Genomic instability was assessed in 5 cases, 3 of them associated with LOH. The only case of gastric cancer that did not show LOH or instability at 5q21 was a stage II, poorly differentiated intestinal carcinoma without evidence of recurrence after a 36 month follow-up period (the mean survival rate in our series was 28.3% at 36 months). We also found LOH in 2/6 dysplastic lesions and 1/4 intestinal metaplasias. Our data show that LOH at 5q21 is frequent in gastric cancer and is also present in intestinal metaplasia and dysplastic lesions. LOH at this locus is not a prognostic factor in GC in our study, due to the high incidence of LOH that we found.

Adult↗
PubMed1996

Tall cell variant of papillary thyroid carcinoma: a reassessment and immunohistochemical study with comparison to the usual type of papillary carcinoma of the thyroid.

A review of 92 consecutive cases of papillary thyroid carcinoma diagnosed at The Methodist Hospital revealed 11 tall cell variant (TCV) cases in nine women and two men. There was a greater average age and larger tumor diameter of TCV cases compared with papillary thyroid carcinoma of the usual type (UPTC), but these differences were not statistically significant. Extrathyroidal extension of tumor was noted in nine of 11 TCV cases and was intraoperatively evident in five cases. The presence of extrathyroidal extension represented a statistically significant difference between TCV and UPTC (p = 0.0001) in a multivariate stepwise logistic regression analysis, with controls for variables of age, sex, tumor size, and lymph node metastases. In 11 TCV patients, tumor recurrence was present in two cases, and there was one tumor-associated death with 1 to 4 years of follow-up. Immunohistochemical stains for thyroglobulin, vimentin, keratins, and Leu-7 were positive in all TCV cases and in 16 of 16 UPTC. Immunoreactivity with antibodies to Leu M1 antigen, a myelomonocytic marker included in cluster designation group (CD 15), which is present in many adenocarcinomas, was present diffusely in all TCV, in contrast to UPTC (with sparse immunostaining in only one of 16 cases). Immunoreactivity with antibodies to ZC-23, an anti-carcinoembryonic antigen (CEA) monoclonal antibody with cross-reactivity to nonspecific cross-reacting antigen and biliary glycoprotein antigen, was present in all TCV but was not present in UPTC. COL-1, a CEA-specific monoclonal antibody, was nonimmunoreactive with all TCV and UPTC cases. Epithelial membrane antigen (EMA) was present in all TCV but was also present focally in eight of 16 UPTC, sometimes in a membranous pattern in epithelium surrounding cystic or hemorrhagic spaces. Strong immunoreactivity with antibodies to Leu M1 and EMA in papillary carcinomas of the thyroid has been associated with advanced stages of disease and tumor-associated mortality. The pattern of immunoreactivity in TCV is dissimilar to that in UPTC and is supportive evidence that TCV is a neoplasm that is distinct from papillary thyroid carcinoma of the usual type.

Adult↗
PubMed1996

Chromosome imbalances in papillary renal cell carcinoma and first cytogenetic data of familial cases analyzed by comparative genomic hybridization.

We used comparative genomic hybridization to analyze 17 tumor samples from 11 patients with papillary renal cell carcinoma (RCC), including three patients with hereditary papillary RCC. Whereas the most frequent aberrations confirmed data obtained by banding analyses, copy number increases on 5q, which previously were considered characteristic of nonpapillary RCC, were identified in two cases. In two complex cases belonging to the same family, a characteristic pattern of chromosomal aberrations was found: five of the six imbalances present in the less complex case were included in the karyotype of the other case, suggesting a genetically determined mechanism resulting in genomic instability of specific chromosomes or chromosomal subregions and/or selection of specific mutations.

Adult↗
PubMed1996

Infarcted myxoid fibroadenoma following fine-needle aspiration.

Infarction of breast fibroadenomas is very rare and is frequently associated with physiologic changes, such as pregnancy and lactation. We report a case of an infarcted fibroadenoma following fine-needle aspiration. The patient presented with an asymptomatic breast mass, which was clinically difficult to evaluate. Excisional biopsy was performed 7 days after a nondiagnostic fine-needle aspiration of the mass. Microscopically, the nodule showed features of a classic fibroadenoma of the intracanalicular type with myxoid or mucinous stromal changes, as well as extensive areas of acute infarction. This report provides another example of the changes that may be observed in biopsy specimens obtained after fine-needle aspiration of the breast.

Adult↗
PubMed1996

A prospective controlled study of luteal and endometrial abnormalities in an infertile population.

OBJECTIVE: To investigate whether luteal and endometrial abnormalities occur more frequently in an infertile population and thus contribute to infertility. DESIGN: Prospective controlled clinical study. SETTING: Outpatient clinic in an academic research institution. PARTICIPANTS: Thirty-three fertile controls and 31 infertile women without ovulatory disorders, tubal disease, or male factors. INTERVENTIONS: All women underwent an endometrial biopsy 9 days after the LH surge followed by an IM injection of 5,000 IU hCG. Blood samples were drawn immediately before hCG administration for serum P and placental protein 14 (PP14) measurements, at 6 hours after hCG stimulation for serum P concentrations, and on day 5 after hCG administration for serum PP14 levels. MAIN OUTCOME MEASURES: Histologic dating of the endometrium and serum P and PP14 measurements. RESULTS: Abnormal endometrial biopsies occurred more frequently in infertile (43%) than in fertile women (9%). Except for one case, these specimens were not associated with low hCG-stimulated P levels. Serum PP14 measurements varied widely and did not discriminate subjects with abnormal endometrial development. CONCLUSIONS: Disruption of endometrial maturation without a concomitant defect of the corpus luteum occurs more frequently in an infertile population and thus may contribute to infertility.

Adult↗
PubMed1995

Loss of heterozygosity on the short arm of chromosome 8 in male breast carcinomas.

Identification of loss of heterozygosity (LOH) at specific genetic loci in neoplastic cells suggests the presence of a tumor suppressor gene within the deleted region. LOH on chromosome 8p has been identified in colorectal, bladder, hepatocellular, and prostatic carcinomas. Little is currently known about the molecular events occurring during the development of male breast cancer. We studied LOH on chromosome 8p in 23 male breast carcinomas. Five polymorphic DNA markers were used: D8S136 and D8S137 on 8p12-21.3; and D8S254, D8S258, and D8S349 on 8p22. DNA was extracted from microdissected normal and tumor cells obtained from formalin-fixed, paraffin-embedded tissue sections and amplified by the PCR. LOH was identified in 19 of 23 cases (83%) with at least one marker. Seven cases showed LOH only at 8p22, six cases showed LOH only at 8p12-21.3, and six cases showed LOH at both 8p22 and 8p12-21.3. In five of these last six cases, at least one locus was retained between the two deleted regions; thus, the whole short arm of chromosome 8 was not lost in these tumors. Our results show that there are two discrete areas of deletion on chromosome 8p in male breast cancer, suggesting the presence of one or more tumor suppressor genes that may play a role in the development or progression of the disease.

Breast Neoplasms, Male↗
PubMed1995

Identical allelic loss on chromosome 11q13 in microdissected in situ and invasive human breast cancer.

Human breast carcinoma is thought to develop through progressive stages from atypical hyperplasias to in situ carcinoma and finally to invasive and metastatic cancer. In situ breast carcinoma consists of small, isolated neoplastic foci which cannot be selectively studied by conventional methods. In this study, we used tissue microdissection to examine the loss of heterozygosity (LOH) of chromosome 11q13 in both in situ and invasive lesions of the breast, as compared to normal breast epithelium from the same patients. Forty-one cases of sporadic breast cancer were analyzed. Tissue microdissection allows for procurement and PCR-based analysis of small lesions using either frozen or formalin-fixed, paraffin-embedded tissue sections. LOH on chromosome 11q13 was found in 24 of 36 (67%) of the informative invasive breast cancer cases using two polymorphic DNA markers specific for this region (INT2 and PYGM). Twenty-one of the cases which demonstrated LOH in the invasive tumor also contained in situ carcinoma in the same tissue section. Seventy-one % (15 of 21) of the microdissected in situ lesions showed LOH of chromosome 11q13. Every case (15 of 15) of in situ tumor with LOH showed loss of the same allele in the corresponding invasive tumor cells. The results of this study suggest that a tumor suppressor gene located on chromosome 11q13 may play an important role in the early stages of development of sporadic human breast cancer. This finding provides molecular genetic support for the hypothesis that invasive breast cancer arises from in situ lesions.

Alleles↗
PubMed1995

Overexpression of cyclin D mRNA distinguishes invasive and in situ breast carcinomas from non-malignant lesions.

The elucidation of molecular alterations that occur during human breast cancer progression may contribute to the development of preventative strategies. Using in situ hybridizations on a cohort of 94 biopsy lesions, quantitatively increased cyclin D mRNA expression levels were observed in only 18% of benign lesions, which confer no or slightly increased breast cancer risk, and 18% of premalignant atypical ductal hyperplasias, which confer a four to fivefold increase in breast cancer risk. The transition to carcinoma was accompanied by frequent cyclin D mRNA overexpression in 76% of low-grade ductal carcinomas in situ, 87% of higher grade comedo ductal carcinomas in situ and 83% of infiltrating ductal breast carcinomas. The data identify a molecular event that may separate benign and premalignant human breast lesions from any form of breast carcinoma.

Breast Neoplasms↗
PubMed1995

Coexpression of TGF alpha, epidermal growth factor receptor, and P-glycoprotein in normal and benign diseased breast tissues.

Twenty-four normal or benign breast tissues were examined for the expression of transforming growth factor-alpha (TGF alpha), epidermal growth factor receptor (EGFR), and P-glycoprotein, the product of the mdr-1 gene. Specific staining for all three proteins was observed in the majority of the samples. P-glycoprotein staining was present in most (88%), and confined to the lumenal surface of the ductal epithelium. Membranous EGFR expression was observed in epithelial cells in 92% of the specimens and 42% displayed both myoepithelial and epithelial cell staining. TGF alpha staining was intense and uniformly distributed through the cytoplasm (96%). Coexpression of EGFR, TGF alpha, and P-glycoprotein in normal human breast tissues suggests a role for each of those proteins in normal breast physiology. An interaction may be present in normal breast tissue between the EGF receptor pathway and P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

The screening histories of women with invasive cervical cancer, Connecticut.

OBJECTIVES: Each case of a continuous series of invasive cervical cancer cases was studied with a structured review procedure conducted by an expert panel to assess the reason that it was not detected before it became invasive. METHODS: All cases of invasive cervical cancer diagnosed in a 5-year period among Connecticut residents were identified; a screening history and screening outcome were obtained for 72% (481 of 664). RESULTS: Two hundred fifty women (51.9%) had suboptimal screening. One hundred thirty-seven women (28.5%) had never had a screening test, and their mean age was greater than that of the rest of the study population (64.5 years vs 46.5 years). Of the 344 women who had ever had a Pap test, 113 (32.8%) had their last Pap test 5 or more years before their diagnosis of invasive cancer; 52 (15.1%) were not followed up properly; 33 (9.6%) had their last smear misread as normal; and 118 (34.3%) developed cervical cancer within 3 years of their last Pap test. CONCLUSIONS: Physicians, nurses, and other care providers need to ensure that woman have timely and accurate screening with proper follow-up, make increased efforts to reach older women, and improve quality control of Pap smear readings.

Adenocarcinoma↗
PubMed1995

Tumor angiogenesis in advanced stage ovarian carcinoma.

Tumor angiogenesis has been found to have prognostic significance in many tumor types for predicting an increased risk of metastasis. We assessed tumor vascularity in 43 cases of advanced stage (International Federation of Gynecologists and Obstetricians stages III and IV) ovarian cancer by using the highly specific endothelial cell marker CD34. Microvessel counts and stage were associated with disease-free survival and with overall survival by Kaplan-Meier analysis. The plots show that higher stage, higher average vessel count at 200x (200x avg) and 400x (400x avg) magnification and highest vessel count at 400x (400x high) magnification confer a worse prognosis for disease-free survival. Average vessel count of less than 16 (400x avg, P2 = 0.01) and less than 45 (200x avg, P2 = 0.026) suggested a better survival. Similarly, a high vessel count of less than 20 (400x high, P2 = 0.019) conferred a better survival as well. The plots suggest that higher stage, higher average vessel count at 200x and 400x, and highest vessel count at 200x and 400x show a trend to worse overall survival as well. With the Cox proportional hazards model, stage was the best predictor of overall survival, however, the average microvessel count at 400x was found to be the best predictor of disease-free survival. These results suggest that analysis of neovascularization in advanced stage ovarian cancer may be a useful prognostic factor.

Adolescent↗
PubMed1995

Effects of aging on menstrual cycle hormones and endometrial maturation.

OBJECTIVE: To investigate changes in menstrual cycle hormones and endometrial maturation that may contribute to the decline in fertility with aging. DESIGN: Prospective controlled clinical study. SETTING: Normal human volunteers in an academic research institution. SUBJECTS: Women with regular menstrual cycles. INTERVENTIONS: Thirty-two women, aged 20 to 30 or 40 to 50 years, had daily blood drawing starting on cycle day 6 to 10 and continuing until 2 days after the onset of next menses. In addition, 60 women, aged 20 to 30 or 40 to 50 years, had a total of 93 endometrial biopsies performed on day 7 to 9 after the LH surge. MAIN OUTCOME MEASURES: Serum LH, FSH, E2, inhibin, P, and placental protein 14 (PP14) levels and histologic maturation of the endometrium. RESULTS: Serum FSH levels were increased whereas inhibin concentrations were reduced in the luteal-follicular transition of women > 40 years. No other hormonal changes were seen in this population, including P and PP14 secretion. Disruption of endometrial maturation occurred at a similar frequency in both age groups. CONCLUSIONS: Follicular recruitment, but not luteal function or endometrial maturation, is disturbed in cycling women > 40 years and may contribute to the decline in fertility with aging.

Adult↗
PubMed1994

Is c-erb B-2 a predictor for recurrent disease in early stage breast cancer?

PURPOSE: To assess the prognostic importance of c-erb B-2 expression in early stage breast cancer. METHODS AND MATERIALS: Immunohistochemical analysis for c-erb B-2 over-expression was retrospectively performed on 107 paraffin-embedded specimens of women with Stage I or II breast cancer entered in a randomized trial. Results were correlated with known prognostic factors such as pathologic axillary involvement, T-size, estrogen and progesterone receptor status, and nuclear grade. Immunohistochemical staining for c-erb B-2 protein expression was also correlated with breast/chest wall failure as well as survival without evidence of disease (NED) and overall survival. RESULTS: C-erb B-2 overexpression was positive in 21% of the biopsy specimens. A significant association was found between c-erb-2 positivity and lesions containing an intraductal component, with 62% of lesions staining positively for c-erb B-2 having an intraductal component compared to only 36% of lesions with an intraductal component staining negatively for the c-erb B-2 protein (p2 = .031). A significant correlation between c-erb B-2 protein over-expression and axillary nodal status, primary tumor size, nuclear grade, and estrogen and progesterone receptor status was not identified. Cox proportional hazards model did not show a significant effect of c-erb B-2 expression for NED or overall survival. CONCLUSION: Our study did not find over-expression of c-erb B-2 to reliably predict for recurrent disease in early stage breast cancer. This data can be added to other series comparing erb B-2 expression and disease outcome among node-positive and node-negative women with carcinoma of the breast.

Adult↗
PubMed1994

The use of molecular genetic analysis in the diagnosis of renal cell carcinoma.

The most common genetic aberration seen in nonpapillary renal cell carcinoma is believed to be the loss or inactivation of allelic material on the short arm of chromosome 3 (3p). Two patients underwent nephrectomy at our institution, each initially receiving a histologic diagnosis of renal cell carcinoma. Molecular analysis of these tissues revealed no genetic deletion on 3p, prompting further histologic and immunohistochemical evaluation of the original specimens. These additional studies confirmed alternate histologies other than renal cell carcinoma in each case. These data suggest that the loss of genetic material on the short arm of chromosome 3 may be specific for nonpapillary renal cell carcinoma. Molecular analysis may prove to be a useful adjunct in establishing the diagnosis in renal neoplasms with equivocal histologies.

Adult↗
PubMed1994

Immunohistochemical analysis of cathepsins D, B, and L in human breast cancer.

Cathepsins D, B, and L are acidic lysosomal proteinases involved in intracellular protein turnover. Increased levels of these enzymes have been reported to be indicators of aggressive tumor behavior in human and rodent tumors. In breast cancer increased levels of cathepsin D have been reported to be an independent prognostic factor in women with stage I disease. We used standard immunohistochemical techniques on formalin-fixed, paraffin-embedded tissue to examine the levels of cathepsins D, B, and L in 80 carcinomas of the breast and compared that with other indicators of aggressive tumor behavior, including stage of disease, tumor size, nuclear grade, estrogen receptor status, disease recurrence, and 5-year survival rates. Positive granular cytoplasmic staining was detected for cathepsin D in 90% of the tumors, for cathepsin B in two thirds of the tumors, and for cathepsin L in approximately one half of the tumors. Positive staining also was seen in normal breast epithelium, areas of apocrine metaplasia, stromal fibroblasts, and macrophages. Our results did not show a correlation between the expression of cathepsins D, B, and L and other indicators of aggressive tumor behavior. We conclude that the results obtained using polyclonal anticathepsin antibodies do not support the prognostic usefulness of immunohistochemical analysis of these three proteinases in tumor cells in human breast cancer.

Adult↗