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We verified the variations of primary tumour steroid receptor status and proliferative activity at different times and phases (follicular vs luteal) of the menstrual cycle and their relationship with short clinical outcome in a cohort of 248 N- breast cancer patients. Steroid receptor content (ER and PgR) was evaluated by DCC assay and proliferative activity by 3H-Thymidine autoradiographic assay (TLI). Median age was 44 years, 60% of tumors were T1, and cytohistological grade was G1-2 in 54% of cases. At surgery, 57% were in the luteal phase while 43% were in the follicular phase. No significant variations were found in mean TLI or ER and PgR characteristics of the primary tumors surgically treated in different periods of the menstrual cycle; however, the ER level resulted significantly higher in 4th with respect to the 3rd week of menstrual cycle, while PgR level was higher in PgR+ cases treated during the 3rd week. The number of relapses and disease-free survival curves after 36 months median follow-up did not differ significantly for patients treated in different periods of the menstrual cycle (12% and 9% of disease relapses in luteal and follicular phases; p=n.s.). We can conclude, therefore, that TLI, ER and PgR expressions could vary significantly during menstrual cycle only in certain specific tumor subgroups.

The polymerase chain reaction (PCR) has been successfully employed for the laboratory analyses of genetic and infectious disorders using DNA extracted from paraffin-embedded tissues. However, fixative type and fixation time influenced PCR reactions and in some circumstances amplification fragments could not be efficiently generated. In this study, we determined the effects of three commonly used fixatives including ethanol, formalin and Histochoice, on the PCR amplification of DNA from paraffin-embedded breast cancer tissue. The effect of fixatives and fixation times was measured by the ability of the extracted DNA to serve as a template for the amplification of 280 and 530 base pair DNA fragments. On amplifying DNA, positive reactions were uniformly seen in the ethanol specimens. The next best fixative was Histochoice with positive results almost constantly observed in the PCR reactions performed. Formalin fixation sometimes compromised DNA amplification. Our results are consistent with previous reports investigating the effect of ethanol and formalin fixation on DNA amplification by PCR. Moreover, this is the first study showing that paraffin-embedded tissues fixed with Histochoice can be efficiently used for PCR gene amplification.

Kaposi's sarcoma (KS) is a multifocal neoplasm of unknown origin. All forms of KS are composed of spindle-shaped cells with elongated nuclei and sheets of endothelial-like cells. The proliferation of spindle cells is accompanied by the presence of an inflammatory infiltrate composed predominantly of T-cells. It has been suggested that this infiltrate might consist of a virally stimulated clonal population of T-lymphocytes which can produce growth factors initiating and substaining the proliferation of spindle-shaped cells. In this study we analyzed for clonal T-cell receptor gama gene rearrangements the T-cell populations present in the cutaneous infiltrate of seven cases of classical Kaposi's sarcoma using a polymerase chain reaction-based approach. Our data demonstrate the lack of a significant clonal population of T-cells in the cutaneous infiltrates of KS. This finding is indicative of a reactive polyclonal response of T-cells to the spindle-shaped cells and supports the contention that spindle-shaped cells are pathogenetically the central cell type in the disease. Our data also indicate that the anti-KS T-cell response, being polyclonal in nature, does not result from clonal expansion of T-cells targeting tumor-associated antigenic peptides.

Aims and Background: The presence of early metastases to distant sites in breast cancer patients is an infrequent event whose mechanisms are still not clear. The aim of this study was to evaluate the biologic and clinical role of DNA ploidy and cell nuclear grade of primary tumors in the metastatic process of a series of stage IV previously untreated breast cancer patients with only visceral metastases., Methods: DNA flow cytometry analysis on paraffin-embedded material and cell nuclear grading of primary tumors was performed on a series of 50 breast cancer patients with only visceral metastases at the time of initial diagnosis., Results: Aneuploidy was found in 28/46 (61%) of evaluable cases and was independent of site of involvement, clinical response, time of progression and overall survival of patients. Of the 46 cases evaluable for nuclear grade, 5 (11%), 16 (35%) and 25 (54%) were classified as G1 (well-differentiated) G2 and G3, respectively. Nuclear grade also was unrelated to response to therapy and overall survival, whereas time to progression was significantly longer in G1-2 than G3 tumors with the logrank test (P < 0.03) and multivariate analysis., Conclusions: Our results seem to stress the difficulty to individualize different prognostic subsets from a series of breast cancer patients with only visceral metastases at initial diagnosis according to DNA flow cytometry and nuclear grade.

In order to observe receptor expression (ER and PgR) in human breast cancer cells during the S-phase of the cellular cycle, we evaluated 21 tumoral samples using a double labeling immunocytochemical-autoradiographic assay. In 16 of these we have verified that expression of ER and PgR is not influenced by incubation with 3H-Thymidine for 60 minutes. The results also demonstrated that receptor expression during the S-phase is more common in postmenopausal tumors and is principally dependent on percentages of ER+ (p < 0.01) and PgR+ (p < 0.01) cells; moreover, proliferative activity occurs almost exclusively in ER- (p = 0.003) and Pgr- (p = 0.001) cellular sub populations and the presence of PgR, but not of ER, is related to arrest of DNA synthesis (p = 0.02).

Clinical and pathological features of five cases of infiltrating cribriform carcinoma (ICC) of the breast observed between 1990 and 1994 are reported. Using histological criteria by Page et al., three cases of pure ICC and two cases of mixed ICC were identified. In the mixed forms, the cribriform component made up about 80% of the neoplasm. After clinical follow-up, from one to five years long, no relapses, axillary lymph nodes or distant metastases were found, even in two cases with very large neoplasms (20 cm and 10 cm, respectively). This report confirms that this type of carcinoma has a very favorable prognosis, especially pure and mixed forms with a predominant cribriform component. Clinical and histological features make ICC a peculiar form of breast carcinoma.

Cancer is often associated with abnormal activation of coagulation leading to a prothrombotic state. Some chemotherapeutic agents used for cancer may induce thrombosis but their biological alterations in the hemostatic system are not yet well understood. This study evaluated alterations of coagulative and fibrinolytic parameters following chemotherapy. In plasma samples of 38 patients (median age: 49 years) receiving CMF (schedule 1-21 or 1-8) for Stage II breast cancer, we evaluated: PT, aPTT, antithrombin III (AT-III), protein C (PC), protein S (PS), thrombin-antithrombin complex (TAT), prothrombin fragment F 1 + 2 (F 1 + 2), fibrinogen (Fbg), tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1) and D-dimer (D-D). PT, aPTT, and Fbg were determined with routine methods; AT-III, PC, and PS were measured with coagulative tests; PC and PS were also evaluated with immunoenzymatic methods, t-PA, PAI-1, D-D, TAT, and F 1 + 2 were measured with immunoenzymatic methods. All tests were performed immediately before starting therapy and after each cycle. A PC antigen decrease appeared soon after beginning therapy and lasted throughout chemotherapy. The lowest values were present after the first treatment both in the CMF 1-21 group (mean +/- SD = 72.5 +/- 10.8%) and in the CMF 1-8 group (mean +/- SD = 77.2 +/- 6.9%): PC activity was also decreased. PS antigen decreased after the first administration (mean +/- SD = 73.3 +/- 10% in CMF 1-21 group, and 72.5 +/- 4.9% in CMF 1-8 group): PS activity also decreased. PAI-1 antigen levels increased (mean +/- SD = 43.1 +/- 20.4 ng/ml in the CMF 1-21 group, and 37.5 +/- 12.2 ng/ml in CMF 1-8 group) lasting up to the last cycle. CMF provokes a trend toward hypercoagulability; this effect should be considered when chemotherapy is employed in advanced cancer patients at high risk for thrombosis, or in patients with other risk factors.

Mucin-like carcinoma-associated antigen (MCA) is a new tumor associated antigen expressed on breast cancer cells independent of histological type and recognized by a two-site sandwich EIA (Roche) using the Mab b-12 as capture and detection antibody and a MCA cut-off of 11 U/ml. MCA serum levels were determined in 409 breast cancer patients and in 100 pts with benign breast disease histologically confirmed and staged according to UICC. The sensitivity of MCA regarding the stage of disease was elevated only in metastatic patients (89%) and the MCA values of this group were significantly different compared to those of patients with early or locally advanced breast cancer. In the group of benign patients, the specificity was 81%. The correlation between MCA values and number of involved axillary lymph nodes showed significant differences in the O versus 4-10 node subgroup (p < 0.001), in O versus > 10 and in 1-3 versus 4-10 node subgroup (p < 0.05); elevated MCA sensitivity was found in the 4-10 and > 10 subgroups. In our experience, the determination of MCA is not useful for early diagnosis of breast cancer nor does it indicate the extent of lymph node involvement. With regard to the prediction of tumor recurrence in postoperative patients free of disease, MCA levels increased concomitantly with the clinical evidence of relapse. These findings suggest that the MCA assay is highly sensitive only in patients with metastatic breast cancer; therefore one of the most promising test application seems to be for monitoring the clinical course of advanced disease patients.

Aims: A comparative analysis was performed to verify a possible correlation between mammographic features and morphobiologic characteristics of the tumor in a series of 176 invasive primary breast cancer patients., Methods: Breast cancers were grouped according to mammographic features as follows: tumor mass with spiculated borders; tumor mass with well-circumscribed borders; tumor with density alteration of parenchyma with no clear borders; a cluster of microcalcifications as the only sign of tumor presence; tumor without mammographic abnormality. The tumor tissue biologic characteristics investigated were: hormone receptor content, tumor proliferative activity, DNA content and cytohistologic tumor-grade differentiation., Results: Spiculated tumors showed a significantly higher percentage of estrogen-receptor-positive cases with respect to circumscribed tumors, independently of the patient's menopausal status. Tumors with only microcalcifications were all from premenopausal patients and showed a significantly higher percentage of progesterone-receptor-positive cases (83%). Tumor proliferative activity did not significantly differ in the 5 mammographic breast cancer groups; aneuploidy was less frequent in tumors with spiculated borders than in mammographic types (39% vs 57%; p = 0.05); percentages of G1-G2-G3 tumors did not differ significantly among the mammographic groups considered., Conclusions: Certain relationships between mammographic features and biologic characteristics could be of potential clinical interest and stimulate more detailed studies on this issue.

To investigate the relationships between the mammographic aspects (according to Broberg), proliferative activity and hormone receptor status, we studied 165 patients subjected to radical mastectomy for operable breast cancer. The highest percentage of estrogen receptor-positive cases was observed in mammograph class I (p < 0.02) while classes III and V were highest in progesterone receptor-positive cases. Proliferative activity (111 cases) was significantly lower in class I and IV with respect to all other classes (p < 0.03 and p < 0.01, respectively). This study suggests that certain mammographic signs can be related to the biological characteristics of breast cancer.

To verify the relationship of mammographic (Mx) patterns of breast cancer to hormone receptor content (ER, PgR) we studied 129 women (59% in postmenopause; average age 55) in the last 3 years. All women had operable breast cancer and were submitted to mammography before surgery. The tumors were classified, according to Mx characteristics, in 5 classes (Broberg, 1983). ER and PgR contents (cut-off for positivity: 10 fmol/mg prot cyt) were analyzed in all patients by means of DCC method. The percentage of ER+ cases was significantly higher in class I than in all other Mx classes (85% vs 57%; p = 0.02), whereas it was lowest in class IV (51% vs 70%; p = 0.03). The percentage of PgR+ cases was significantly different only in class I with respect to class IV (70% vs 41%; p = 0.002). As for ER and PgR mean tumor content, no statistically significant difference was observed between the 5 classes. When the 2 receptors were simultaneously considered the percentage of ER+ PgR+ cases was higher in class I than in all the extant classes (p = 0.01), and the percentage of ER- PgR- was higher in class IV than in the extant ones (p = 0.02). In selected subgroups of patients, Mx classification of breast cancer can help the physician predict the hormone receptor tumor status with sufficient reliability.

From January 1985 to September 1988, 60 women with advanced breast cancer were randomized in two arms to receive: A) tamoxifen (TAM) (20 mg/die) until progression or B) TAM (20 mg/die for 14 days) then medroxyprogesterone acetate (MPA) (1500 mg/die p.o. for 14 days) followed by 7 days of wash-out before repeating the TAM/MPA treatment. All patients were post-menopausal, previously untreated with hormone therapy, and with tumor receptor status determined immediately before randomization; all had objectively evaluable lesions. In order to verify hormone receptor variations due to the antiestrogen, when possible a second biopsy was performed after the initial 14 day cycle of TAM. Thirty-one and 29 patients were included respectively in arms A and B. Objective regression (CR + PR) was observed in 58% of group A and 75% of group B, with CR in 11% and 23%, respectively. Differences were not statistically significant. Median time to progression was 12 months for group A and 9 for group B. Overall survival has not yet been reached in group A while it was 34 months for patients of group B. Metrorrhagia was observed in two cases of group A and in 6 of group B, and thrombophlebitis in 1 and 3 cases, respectively. The second biopsy confirmed a clear increase of PgR content in 8/11 cases (75%). Plasma level variations of TAM, N-desmethyl TAM and MPA were checked at various intervals on 3 patients of group B, and confirmed that our schedule is able to produce a drug wash-out period for tumor cells. In conclusion, our study demonstrated that while the manipulation of hormone receptors seems possible, results indicating better overall survival and time to progression were not obtained with alternate sequential TAM-MPA therapy.

Surgical patients have a high risk of infections. In the breast surgery, a "clean" surgery, the infection rate should not be more than 2%. In this work, we have studied 174 women with breast cancer, which did not receive the antibiotic prophylaxis. After surgery the patients were monitored for infective complications. The total incidence of infections was 5.1%: 3.4% of surgical wound infections and 1.7% of nosocomial infections. The preoperative antibiotic therapy should not be used in the "clean" surgery, as the mastectomy, except in the patients with high infective risk. In fact we can prevent the wound infections of breast surgery with adequate control measures about the aseptic procedures of operating suite, the members of the surgical team and the preparation of the patient.