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Biomedical subjects

I Nenci

Publications and source records attributed to I Nenci.

At least 19 recordsLinked to original sources
PubMed1992

Clinical usefulness of estrogen receptor immunocytochemistry in human breast cancer.

We assessed the reliability of the immunocytochemical assay of estrogen receptor (ER-ICA) as a marker of clinical outcome. Relapse-free interval (RFI) and overall survival (OS) according to ER-ICA status were retrospectively evaluated on a series of 210 patients who had undergone surgery for primary breast cancer between January 1985 and December 1988. ER assay by the dextran-coated charcoal method (DCC) was also performed in 189 tumors. A significant positive correlation was found between the DCC and ER-ICA assays, with an overall agreement of 79%. ER-ICA status showed a prognostic predictive power with respect to OS and RFI in the whole series of patients and in the subset of node-positive patients. It was also a marker of outcome with respect to OS in the subsets of node-negative patients and patients with tumors < or = 2 cm in diameter. Moreover, the predictive value of the ER-ICA assay was higher than that of the DCC assay in the present study. These findings emphasize the clinical usefulness of the ER-ICA assay as a measure for prognosis.

Adult↗
PubMed1992

Chemotherapy versus tamoxifen versus chemotherapy plus tamoxifen in node-positive, oestrogen-receptor positive breast cancer patients. An update at 7 years of the 1st GROCTA (Breast Cancer Adjuvant Chemo-Hormone Therapy Cooperative Group) trial.

504 evaluable node positive oestrogen receptor (ER) positive breast cancer patients were randomly allocated to receive either 5 years tamoxifen treatment or chemotherapy [six courses of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) followed by 4 courses of epirubicin] or a combination of both treatments. At a median follow-up of 5 years tamoxifen appeared to be more effective than chemotherapy, the difference being highly significant in postmenopausal women. The addition of chemotherapy to tamoxifen was not able to significantly improve the results achieved by tamoxifen alone, irrespective of menopausal status. Trends were similar even after stratification for the number of involved nodes. The protective effect of tamoxifen in terms of reduction of the odds of death increased with time and no rebound phenomena on recurrence or death has occurred so far after the completion of tamoxifen treatment. Overall, the prognostic value of number of involved nodes and of progesterone receptor (PgR) status was confirmed by multivariate analysis. However, the predictive value of PgR was lost in patients receiving tamoxifen alone. Similarly, the degree of ER positivity was not predictive of the response to tamoxifen. Tamoxifen treatment should still be regarded as the gold standard for postmenopausal ER positive patients. In younger women the antioestrogen proved to be safe and at least as effective as chemotherapy. However, the analysis of the annual risks suggests that the concurrent or the sequential use of chemotherapy and tamoxifen might represent a more appropriate treatment for this patient subset, particularly for those with four or more involved nodes. Different cut-offs of ER and PgR assays from those we have arbitrarily employed in the present analysis should probably be used to select more properly the patients who can benefit from endocrine therapy.

Adult↗
PubMed1992

Suppression of tumorigenesis by the breast cancer cell line MCF-7 following transfer of a normal human chromosome 11.

Breast cancer development is associated with several genetic abnormalities. Loss of heterozygosity in the short arm of chromosome 11 has been observed in 30% of tumors. We found homozygosity at five chromosome 11 polymorphic loci in genomic DNA of the MCF-7 breast carcinoma cell line, suggesting a possible loss of one chromosome 11. We have studied the transformed and tumorigenic phenotypes of MCF-7 cells following introduction of a normal human chromosome 11 via microcell fusion. MCF-7/H11 cell hybrids, containing chromosome 11, showed in vitro characteristics similar to the parental cell line. However, tumorigenicity in athymic mice was completely suppressed. Since tumor formation by MCF-7 cells is estrogen dependent, we have analysed the expression of the estrogen receptor and of the estrogen-activated gene pS2. No difference was detected between the parental MCF-7 cells and the derived chromosome 11 cell hybrids, indicating that the mechanism of MCF-7 tumor suppression by chromosome 11-associated functions does not directly involve the estrogen/estrogen receptor molecular pathway.

Animals↗
PubMed1991

Linkage of biopsy, cancer, and population records aimed at the estimation of family risks in neoplasia: a pilot study.

STUDY OBJECTIVE: The aim was to link individual demographic and medical records into sibships to obtain the sibling distribution of biopsies and cancers, and thereby calculate heritability and recurrence risks in families, thus aiding early diagnosis and prevention of cancers. DESIGN: The 157,823 individual records of the inhabitants of the town of Ferrara in Italy were automatically linked into 106,821 sibships. A 10% sample (10,842 sibships) was then extracted from the distribution of sibships and tabulated, for linkage to medical records. PATIENTS: The biopsy records at the Institute of Pathological Anatomy of the University of Ferrara were manually linked to cancer records and then to sibships. It was possible to construct the distribution of 2062 biopsies and of 829 cancers in sibships. RESULTS: From the distribution of biopsies and tumours in sibships, it was possible to estimate the incidence of tumours in the population (0.052) and in siblings of affected (0.083), and to apply to such distributions current methods for the estimate of heritability (h2 = 0.246) and of recurrence risks of tumours in sibships, age independent. CONCLUSIONS: The study shows that the procedure resulting in the estimation of incidences and recurrence risks for tumours could be completely automated, and extended to whole populations and homogeneous subgroups in post industrial cultures.

Biopsy↗
PubMed1990

Immunohistochemical expression of c-erbB-2 in human breast cancer by monoclonal antibody: correlation with lymph node and ER status.

c-erbB-2 Protein expression was investigated in a series of fifty primary breast cancers by means of a specific monoclonal antibody and immunocytochemistry. Specific staining was observed at the plasma membrane level of neoplastic cells, according to the reported localization of c-erbB-2 protein. Sixty-four percent of tumors scored positive, with a variable amount of stained cells. The rate of protein expression was found to exceed the reported gene amplification. No relationship was observed between c-erbB-2 protein staining and age, menopausal status or histologic subtypes. An inverse association was found between c'erbB-2 protein staining and estrogen receptor content of tumors, assayed by immunocytochemistry. A positive relationship was observed between c-erbB-2 protein expression and presence of axillary node metastasis. These findings suggest that c-erbB-2 protein expression is a marker of tumor aggressiveness and that its prognostic power deserves further investigation both in node-positive and node-negative patients.

Adult↗
PubMed1990

Chemotherapy versus tamoxifen versus chemotherapy plus tamoxifen in node-positive, estrogen receptor-positive breast cancer patients: results of a multicentric Italian study. Breast Cancer Adjuvant Chemo-Hormone Therapy Cooperative Group.

Between November 1, 1983 and June 30, 1987, 510 node-positive, estrogen receptor (ER)-positive breast cancer patients have been randomly allocated to receive either chemotherapy (six intravenous [IV] cyclophosphamide, methotrexate, and fluorouracil [CMF] courses followed by four IV epirubicin courses) or 5 years of tamoxifen treatment or a combination of both therapies. After a median follow-up of 40 months, patients receiving the combined treatment achieved the best results, and those treated with chemotherapy alone achieved the worst, the difference being particularly evident in postmenopausal women. However, while the concurrent use of chemotherapy and tamoxifen did improve the results achieved by chemotherapy alone, particularly in postmenopausal women and in those with four or more involved nodes, it did not significantly improve the results achieved by tamoxifen alone, particularly in patients with higher ER tumor concentrations. Side effects were more numerous and more severe in patients receiving chemotherapy (with or without tamoxifen). Our findings, although still preliminary, confirm that tamoxifen should be the treatment of choice for postmenopausal breast cancer patients with node-positive, ER-positive tumors. In addition, the findings suggest that tamoxifen may represent a safe alternative to chemotherapy (at least to the cytotoxic regimen we used) for younger women, provided they have ER-positive tumors. In patients with ER-positive tumors, the addition of chemotherapy to tamoxifen does not seem to improve significantly the effectiveness of tamoxifen alone.

Adult↗
PubMed1990

Assessment of proliferative rate of breast cancer by Ki-67 monoclonal antibody.

The proliferative activity of 163 primary breast cancers was assessed by immunocytochemistry with the mouse monoclonal antibody Ki-67, which recognizes a nuclear antigen expressed in all phases of the cell cycle except for Go. The overall frequency distribution of Ki-67 staining was of exponential type, with percentage of positive staining cells ranging from 0.3 to 88.3%, with a median value of 10.1%. No relationship was observed between Ki-67 values and menopausal status of patients. A significant positive correlation was found between Ki-67 values and tumor grade, especially mitotic grade. Estrogen Receptors (ER) were assayed by immunocytochemistry with ER-ICA method and by dextran-coated charcoal method (DCC) in 129 and 141 tumors, respectively. A negative correlation was found between the ER content by both methods and Ki-67 score. Eighty-nine percent of cases with Ki-67 value less than 10.1% contained more than 10% ER-ICA-positive cells. Progesterone receptors (PgR) were assayed by immunocytochemistry with PgR-ICA method and by DCC in 62 and 141 tumors, respectively. A negative correlation was observed between the PgR content by both methods and Ki-67 score. No correlation was found between Ki-67 score and lymph node involvement by tumor. These findings suggests that Ki-67 score could be used as an independent prognostic marker, useful to distinguish different risk for recurrence within the two clinically heterogeneous groups of N- and N+ patients.

Adult↗
PubMed1989

Monoclonal antibodies for specific immunoperoxidase detection of Campylobacter pylori.

Monoclonal antibodies were raised against Campylobacter pylori to detect the organism in clinical specimens by the immunoperoxidase technique. Twenty-one hybridoma cultures obtained were screened on tissue sections of gastric mucosa to identify antibodies that did not cross-react with host cells. To select antibodies with high grade of specificity to C. pylori, hybridomas were also screened by an enzyme-linked immunosorbent assay against a wide panel of gram-negative bacteria. Fifteen antibodies showed a variable grade of cross-reactivity with gastric mucosa, indicating the presence of at least three epitopes shared by C. pylori and epithelial cells. Three of the six antibodies non-reacting with gastric mucosa (CB-1, CB-26, and CB-31) also were found to be specific for C. pylori. Using CB-26 in an indirect immunoperoxidase test, gastric brushings from 60 patients consecutively undergoing endoscopic examination were examined. By light microscopy, we observed the presence of large amounts of C. pylori in smears from all the 32 patients with positive culture. A small number of bacterial cells were also seen in 8 of 28 patients whose cultures were negative. These findings suggest that the monoclonal antibody CB-26 might be of value for rapid and specific detection of C. pylori.

Animals↗
PubMed1988

Expression of p21 ras gene products in breast cancer relates to histological types and to receptor and nodal status.

Expression of the p21 product of the ras gene family was investigated in a series of 142 infiltrating primary breast tumors by two specific ras p21 monoclonal antibodies with an immunocytochemical technique. The majority of tumors demonstrated a varying number of positive cells. A significant association between p21 expression and tumor histotype was found: among ductal carcinomas the comedo variety was always positive; conversely, lobular tumors were more frequently negative. Nodal status was recorded for all patients. A significant difference was found in nodal status with respect to p21 expression: tumors with more than 50% positive cells were more often N+. Estrogen receptor (ER) status was determined in 77 tumors. Tumors with higher levels of p21 contained a high percentage of estrogen receptor positive cells. The present results show that p21 expression in human breast cancer could be a marker of tumor aggressiveness and might thus improve the predictive power of known prognostic factors such as estrogen receptor and nodal status.

Breast Neoplasms↗
PubMed1988

Commentary on human mammary preneoplasia. The estrogen receptor-promotion hypothesis.

In the carcinogenic process, promotion is the process whereby an initiated tissue develops focal proliferations which act as proximate precursors. The evidence obtained from the immunocytochemical staining by monoclonal anti-receptor antibodies indicates that the early steps (atypical hyperplasias) in the carcinogenic process of the breast show an increased and homogeneous expression of the estrogen receptor. These observations suggest that the persistent sensitivity to estrogen may be critical in sustaining the growth of mammary preneoplastic changes and their progression to ultimate precursors and to invasive cancer.

Breast Neoplasms↗
PubMed1987

Immunocytochemical demonstration of estrogen receptors by monoclonal antibodies in human breast cancer: correlation with estrogen receptor assay by dextran-coated charcoal method.

Immunocytochemical demonstration of estrogen receptors in 115 human breast cancer specimens was performed using mouse monoclonal antibodies against estrogen receptor and avidin-biotin as the displaying system. The antibody indicated a highly heterogeneous endowment of neoplastic cells with estrogen receptor at both nuclear and cytoplasmic levels. The percentage of labeled cells within each tumor specimen was recorded to compare this immunocytochemical assay with the biochemical assay of estrogen receptors by the dextran-coated charcoal method. A significant correlation was observed between these two assays. The present results show that estrogen receptors can be confidently demonstrated at the single cell level, thus providing additional information to quantitative biochemical assays. Their prognostic and therapeutic predictive powers may be usefully integrated, particularly in view of the heterogeneous distribution of receptors among cancer cells.

Antibodies, Monoclonal↗
PubMed1987

Pathophysiology of estrogen receptors in mammary tissue by monoclonal antibodies.

Identification of preneoplastic lesions of the breast has mainly rested on morphological grounds, supported by epidemiological data. These studies assign a definite precancerous potential to a group of atypical hyperplastic lesions and in situ carcinoma. In spite of much effort no criteria are yet available to understand which, among these lesions, is committed to infiltrative growth, in other words, to understand the risk to a single patient. Estrogens are know to play a critical role in the etiology of breast cancer. The hypothesis is investigated that this role is dependent on a modified expression of their receptor. To approach this question estrogen receptor expression was traced by specific monoclonal anti-receptor antibodies and immunocytochemistry, on a spectrum of breast tissue changes, from normal tissue to infiltrating cancer. Estrogen receptor expression is heterogeneous in normal tissue and in infiltrating cancer, and on the contrary is homogeneous in proliferative atypical lesions and in in situ carcinomas. Present results show that receptor expression is enhanced and becomes homogeneous, maybe constitutive, in atypical hyperplasia and in in situ carcinoma and that this phenomenon could subserve important changes of proliferative capacity which are necessary and possibly sufficient for autonomous growth.

Breast↗
PubMed1985

Expression and modulation of estrogen receptors in human breast cancer.

Estrogen receptors have been traced at the tissue level in premalignant and malignant changes of human mammary gland by an immunoperoxidase technique using a monoclonal antibody against the receptor protein. Proliferative premalignant cells show an increased and homogeneous expression of the estrogen receptor by this technique; it seems that a constitutive expression of the receptor may play a role in the promotional carcinogenetic process. Moreover, infiltrating tumors show a striking heterogeneity in the cellular expression of estrogen receptor, which seems related to differentiation level.

Antibodies, Monoclonal↗