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V Cappelletti

Publications and source records attributed to V Cappelletti.

At least 37 records · Page 2Linked to original sources

Progesterone receptor determination in human breast tumors by immunocytochemical and biochemical techniques.

Progesterone receptors were determined on frozen sections from 74 primary human breast tumors by an immunocytochemical assay using an indirect avidin-biotin peroxidase method. In the same tumors, cytosol estrogen (ERc) and progesterone receptors (PgRc) were determined by ligand binding assay, and nuclear estrogen (ERn) and progesterone receptors (PgRn) were determined by an immunoassay. Immunocytochemical staining was seen in 36% of tumors. It was predominantly nuclear and there was extensive cell to cell heterogeneity. When the immunocytochemical results were compared to PgRc the agreement rate was 63%, but it was 77% when compared to PgRn. About one third (38%) of PgRc positive tumors were immunocytochemically defined as negative. Thus a significant discordance exists between this immunocytochemical assay for PgR and both the conventional radioligand assay (used for PgRc) and the relatively new enzyme immunoassay (used for PgRn). However discordance rates were critically influenced by the arbitrary cutoff levels that were used to define receptor positivity in the biochemical assays. Our studies support the addition to, rather than the substitution of, immunocytochemical methods, to the conventional biochemical assays for PgR, until long-term follow-up studies of patients with PgRn and immunocytochemical PgR determinations become available.

Breast Neoplasms↗

Simultaneous estimation of epidermal growth factor receptors and steroid receptors in a series of 136 resectable primary breast tumors.

Human breast cancer cell lines, as well as human breast cancer biopsies, possess specific high-affinity epidermal growth factor receptors (EGF-r). However, reports on the presence of EGF-r in human breast cancer biopsies are still controversial, especially concerning the relationship between EGF-r and other biological variables whose prognostic relevance is well known, such as the estrogen (ER) and progesterone (PgR) receptors. In the present study, the EGF-r content was estimated in a series of 136 unselected breast cancer primaries along with cytoplasmic (ERc) and nuclear (ERn) ER and cytoplasmic PgR. EGF-binding activity consisted of a single class of high-affinity binding sites (Kd = 0.55 nM) and ranged from 0 to 275 fmol/mg protein. We observed a strong inverse association between EGF-r and ERc (p less than 0.001); in fact, about two thirds of the tumors were ERc-positive/EGF-r-negative or ERc-negative/EGF-r-positive. The same type of association was found between EGF-r and either ERn or PgR. Kendall's rank correlation test confirmed that the EGF-r concentrations were correlated with the levels of ERc (tau = -0.291, p less than 0.0001), ERn (tau = -0.27, p less than 0.0005) and PgR (tau = -0.162, p less than 0.01). The EGF-r content was significantly higher (p less than 0.0001) in the ERc-negative tumors (72.6 +/- 54.4 fmol/mg protein) as compared to the ERc-positive ones (33.0 +/- 37.4 fmol/mg protein). Similarly, the subset of PgR-positive tumors was characterized by lower EGF-r mean concentrations when compared to PgR-negative cases (35.4 +/- 54.4 vs. 63.8 +/- 54.4 fmol/mg protein). These results confirm the previously described inverse relationship between EGF-r and steroid receptors. Moreover, they suggest the existence of an interaction between steroid hormones and EGF and support the need for further studies to better understand their respective roles in modulating breast cancer growth.

Breast Neoplasms↗

Role of cellular retinoic acid binding protein (cRABP) in patients with large bowel cancer.

The presence of cellular retinoic acid binding protein (cRABP) was analyzed in 13 consecutive patients with large bowel cancer (one right colon and 12 rectum-sigmoid, classified as three Duke B, eight C, and two D). Specimens of neoplastic tissue and of adjacent mucosa were obtained at surgery, and cRABP was determined by an assay based on incubation of partially purified cytosol with labeled retinoic acid and ultracentrifugation in sucrose density gradients. Sixty-one percent of tumors contained detectable levels of cRABP, whereas 58.3% of normal mucosal specimens were positive for cRABP. Among the positive tumors 62.5% contained cRABP also in the corresponding mucosa; in the group of cRABP-negative tumors, 40% showed cRABP in the adjacent mucosa. No correlation could be established with the grading or the stage of the tumors; however, interestingly, 100% (three cases) of gelatinous carcinomas were cRABP positive. Since cRABP seems to be a character of neoplastic cells contrary to normal ones, it would be interesting to investigate the conditions that influence the presence of this protein in normal appearing mucosa adjacent to carcinoma.

Carrier Proteins↗

Relationship between ER-ICA and conventional steroid receptor assays in human breast cancer.

We applied a new immunocytochemical assay for estrogen receptors (ER-ICA) to 82 human breast tumors. Results were correlated with cytosolic estrogen receptors (ERc) and nuclear ER (ERn) determined on the same sample respectively by the radioligand binding assay and by an ER enzyme immunoassay (ER-EIA). All ER-ICA-positive tumors contained more than 10 fmol/mg of protein of ERc and were therefore considered as ERc positive. In contrast, 15.4% of ERc-positive cases were ER-ICA negative. Comparison of ER-ICA results with ERn showed extensive agreement of negativity (92%), whereas 38% of ER-ICA-positive tumors were ER-EIA negative. However, the latter had ERc levels above the positivity threshold. Quantitative features of the immunocytochemical staining such as intensity and percentage of labelled cells, considered separately, did not reflect the amount of ERc or ERn. Cellularity was not significantly correlated with ER-ICA and biochemical results.

Breast Neoplasms↗

Comparison of immunochemical and radioligand binding assays for estrogen receptors in human breast tumors.

We have compared a new enzyme immunoassay (EIA) for estrogen receptors (ER) with our conventional radioligand binding assays (multipoint dextran-coated charcoal assay for cytoplasmic ER and hydroxylapatite exchange assay for nuclear ER). Cytoplasmic ERs were measured in 76 human breast cancer specimens by EIA and by five-point Scatchard analysis. The correlation between the two assays yielded a straight line with a slope of 0.92 (r = 0.95; P less than 0.001); conversely, in 31 nuclear salt extracts, linear regression analysis of hydroxylapatite exchange assay data with EIA showed a clear correlation (r = 0.93; P less than 0.001) but a slope of 1.7, demonstrating that EIA detects more ER sites. The binding of the antibody to the cytoplasmic ER molecules was investigated by sucrose density gradient analysis, which showed that EIA recognizes both cytoplasmic forms (9 and 3S), but does not distinguish between them. Advantages and drawbacks of this method are discussed with respect to its application for routine receptor determination for clinical management of breast cancer patients.

Breast Neoplasms↗

Hormone steroid receptor variation after tamoxifen administration in endometrial adenocarcinoma from postmenopausal patients.

Cytoplasmic and nuclear variations of estrogen (ER) and progesterone receptors (PgR) induced by tamoxifen (TAM) treatment were investigated in 38 postmenopausal women with endometrial carcinoma. The treatment consisted of a daily oral administration of 40 mg for 7 days. Tumor samples from each patient were withdrawn before TAM administration under hysteroscopy and at the time of hysterectomy. Cytoplasmic and nuclear receptors were respectively determined by the dextran-coated charcoal assay and the hydroxylapatite technique. In the cytoplasmic fraction no significant change in mean ER value was observed, but a statistically significant increase in PgR was found (P less than 0.001). Conversely, in the nuclear fraction PgR did not vary, but a significant increase in ER content (P less than 0.001) was observed. PgR, analyzed by sucrose density gradient after TAM, showed the same sedimentation property (9 S) as the preexisting receptor, but with a single peak profile, indicating a lower heterogeneity. Our data support the hypothesis that the mechanism of PgR synthesis is induced by the ER-TAM complex and suggest the possibility of increasing the PgR content in these patients for sequential endocrine therapy.

Adenocarcinoma↗

Variations in estrogen and progesterone receptor content in premenopausal breast cancer patients throughout the menstrual cycle.

Estrogen (ER) and progesterone (PgR) receptor content was assayed in 290 premenopausal women with primary breast cancer, in order to investigate the influence of endogenous hormones on cytoplasmic receptor concentrations throughout the menstrual cycle, subdivided into four phases of ovarian function (early and late follicular phase, early and late luteal phase). Of the total population, 231 (79.7%) patients were ER positive and 59 (20.3%) were ER negative; 220 (75.9%) were PgR positive and 70 (24.1%) were PgR negative. The percentages of positive cases were almost constant in each phase. No significant difference in mean values of ER concentration was noted throughout the cycle. Instead, the PgR concentration significantly increased from the first to the third phase (P = 0.02) and decreased from the third to the fourth phase (P = 0.01). Our results suggest that ER- and PgR- cases are homogeneously distributed and not influenced by the phase of the cycle. Moreover, they suggest that PgR measurement in the luteal phase, rather than in other phases, prevents the occurrence of false low PgR levels and, at the same time, improves its prognostic significance and response rate to endocrine therapy.

Adolescent↗

Prognostic significance of progesterone receptors alone or in association with estrogen receptors in human breast cancer.

Estrogen (ER) and progesterone (PgR) receptors were measured simultaneously in 1144 consecutive breast cancer patients to determine the distribution of patients according to receptor and menopausal status when receptor occurrence rates were considered. The prognostic significance of PgR, either alone or in association with ER, was studied on 187 consecutive breast cancer patients treated only by radical mastectomy. All the cases, as regards axillary node status, were pathologically assessed as node negative. These patients did not receive any adjuvant treatment after mastectomy. At 36 months after mastectomy, the follow-up indicated that PgR- patients have a worse prognosis than PgR+ ones. This is evident when PgR alone is considered as a prognostic factor as well as when it is used to identify, within ER+ cases, those with a higher probability of relapse. In conclusion, it can be stated that although PgR status is an independent prognostic factor, it is useful to evaluate ER and PgR simultaneously for better patient management.

Adenocarcinoma↗

Distribution of estrogen and progesterone receptors in primary tumor and lymph nodes in individual patients with breast cancer.

Primary breast cancer tissue and lymph nodes were obtained from 48 patients. Estrogen receptors (ER) and progesterone receptors (PgR) were determined by a dextran-coated charcoal assay. ER were present in 72.9% of the primary tumors and in 62.4% of the malignant lymph nodes, whereas PgR were present in 73.0% and 50.0% of the cases, respectively. The primary tumor and the corresponding malignant lymph nodes showed an identical ER and PgR status, i.e., both tumor sites were receptor positive or both receptor negative in 89.6% and 77.1%, respectively. However, 10.4% of the patients had ER-positive tumors but ER-negative lymph nodes and 22.9% had PgR-positive primaries with PgR-negative lymph nodes. No receptor-positive lymph nodes showed a combination with receptor-negative primary tumor. This preliminary data shows that receptor-positive malignant lymph nodes mostly display the same receptor status as the corresponding primary tumor, whereas receptor-negative lymph nodes may have a receptor-positive primary tumor.

Axilla↗

[Analysis of the enzyme terminal deoxyribonucleotidyl transferase in lymphoma and leukemia cells].

This work analyses the presence of terminal deoxynucleotidyl transferase (TdT) in neoplastic lymphoid cells from a series of malignant lymphomas and in leukemic cells from blood or bone marrow of patients with lymphoproliferative diseases. The studied cases were 63 patients with acute leukemias, 26 patients with chronic leukemias, 85 patients with lymphomas and 14 normal controls. The presence of TdT in the neoplastic cells was determined by optimized assays of enzymatic activity or by immunofluorescence test for TdT positive blasts. The fluorescence tests made use of anti-TdT antibodies specifically absorbed on cells containing the enzyme and then revealed by a second fluorescent antibody. Appreciable amounts of TdT were found in the white cells of blood or bone marrow from the following 25 out of 35 acute lymphoblastic leukemias (ALL) with modulations in the different phenotypes; 13 out of 14 acute undifferentiated leukemias (AUL); and 9 out of 15 blastic crises in chronic myelogenous leukemia (CMLbc). The enzyme was present in 12 out of 14 lymphomas of lymphoblastic type (LL); 2 B lymphoblastic lymphomas did not show any TdT positivity. The highest levels of TdT were detected in cells classified as immature lymphoblast or in their precursors. TdT was absent from normal lymph nodes from leukocytes of chronic lymphocytic leukemia (CLL) and chronic (CML) and acute myelogenous leukemia (AML). 2 out of 14 cases of AML showed a border-line positivity. A definite correlation between concentrations of enzymatic activity and percentage of immunofluorescent cells could not be established. We did not find a precise correlation between the TdT content of lymphoid blasts and other clinical prognostic indices.(ABSTRACT TRUNCATED AT 250 WORDS)

DNA Nucleotidylexotransferase↗

Hormone treatment and sex steroid receptors in metastatic renal cell carcinoma: report of a multicentric prospective study.

Twenty-eight patients with metastatic renal cell carcinoma entered a multicentric prospective study to evaluate the response to high-dose medroxyprogesterone acetate (MPA) and testosterone in MPA failures in relation to sex steroid receptors. No objective remission was seen in the 24 evaluable patients, and only disease stabilizations of short duration were achieved in one-third of treated patients. Stabilizations achieved with second line testosterone were all seen in patients unresponsive to MPA. Receptor studies demonstrated that estrogen, progesterone, or androgen receptors were found in low concentrations and in only 6 of 23 tumors (26%) and 13 normal tissue samples (56%). Surprisingly, no disease stabilization was achieved in patients positive for receptors. It can be concluded that the occasional objective responses to hormone therapy reported in the literature may have been due to some cytotoxic effect of hormone therapy rather than to a true hormonal mechanism.

Adenocarcinoma↗

Adjunctive medroxyprogesterone acetate to radical nephrectomy in category M0 renal cell carcinoma. Preliminary report of a prospective randomized trial.

From July 1979 to December 1981, 83 patients from 6 centers in the Lombardy underwent radical nephrectomy for category M0 renal cell carcinoma. Postoperatively they were randomly allocated to adjunctive medroxyprogesterone acetate (MPA) or to a control group. After the first year of follow-up, the relapse rate was 13% in the controls (5 of 38 evaluable patients) versus 28% in the MPA treatment group (9 of 32). Sex steroid receptors were studied in both the tumor and in the surrounding healthy parenchyma by the dextran-coated charcoal technique in 52 of 70 clinically evaluable patients. There was no significant correlation between receptor studies and the relapse rate. Besides, receptors were more often detected in the healthy than in the neoplastic tissue, and values rarely exceeded 10 fmol/mg protein. Due to the negative trend in the MPA treatment group, the admittance of patients to this study was stopped after 120 patients had been accepted.

Adenocarcinoma↗