p53 gene alterations in special types of breast carcinoma: a molecular and immunohistochemical study in archival material.

The p53 locus on the short arm of chromosome 17 at 17p13.1 was examined for small genomic deletions and mutations in 23 formalin-fixed, paraffin-embedded cases of special types of breast carcinoma (six medullary, seven apocrine, five differentiated tubular, and five papillary). p53 mutations in the evolutionarily conserved exons 5-9 were detected in 11 cases (four apocrine, two papillary, two medullary, and three differentiated tubular), using the novel non-radioactive PCR-based Hydrolink mutation detection enhancement (MDE) method, and confirmed by direct sequencing of the PCR products. Missense mutations causing amino acid substitutions were evenly distributed among exons. One case of apocrine carcinoma showed a polymorphism at codon 213 (CGA-->CGG). Twelve out of 23 cases were found to express a strong nuclear signal against CM-1 and DO-7, two anti-p53-specific antibodies. Small genomic deletions in the vicinity of the p53 locus were detected in 11 tumours (three papillary, three differentiated tubular, two medullary, and three apocrine carcinomas), using the multiplex PCR method. No statistical correlation was found between deletions at 17p13.1 and p53 mutations (P < 0.5). In addition, p53 mutations and immunoexpression correlated with the c-erbB-2 gene product, an oncogenic protein that has been implicated in cell cycle control (P < 0.001). Our findings suggest that genomic alterations of the p53 gene are quite common events associated with special types of breast carcinoma, particularly of the apocrine subtype, but the prognostic value is unlikely to be of clinical importance.

Megalomastia: histological, histochemical and immunohistochemical study.

Megalomastia is a rare entity characterized by an uncommon enlargement of both breasts. Unilateral megalomastia is extremely rare. The purpose of this study was to collect information concerning the history of patients with this condition and to investigate its histology in order to outline the profile of this peculiar entity. Fifty cases of megalomastia were studied. In 41 data concerning the history of the patients was complete; there were 32 juvenile, 7 gravid and 2 adult type cases. All three unilateral megalomastias were in the juvenile group. A family history of megalomastia was frequently present; gravid megalomastia was more closely connected with a maternal familial history. A case of simultaneous megalomastia in monozygotic twins is included. The final size achieved by the breasts was independent of the type of megalomastia, the rapidity of breast development and the body weight of the patients. It was greater in breasts containing abundant adipose tissue and less in fibrous breasts. In all cases of megalomastia associated with pregnancy the breasts had lost the ability to produce milk. The main histological feature in all cases was severe damage and destruction of the lobular units associated with extensive fibrosis. In some breasts of all three types of megalomastia ramified new ducts named "juvenile units" had developed and had proceeded to atrophy. Immunohistochemistry revealed that the epithelium of these units was negative for oestrogen and positive to progesterone receptors. A biphasic pathological appearance, consisting of atrophic lobular units and "juvenile units", is diagnostic of megalomastia.

Tubal conjoined twin pregnancy.

A unique case of tubal conjoined twin pregnancy is reported. The embryos presented a lateral type of conjunction, which also is extremely rare, and were classified as symmetrical iliothroacopagus conjoined twins.

Microcalcifications in breast carcinomas. A histological and histochemical study.

Microcalcification in breast carcinomas were studied histologically and histochemically in 332 prospectively collected mastectomy consecutive specimens, without previous roentgenographic examination. Microcalcifications were found in 41% of breast carcinomas. The incidence was higher in comedo-carcinomas, duct carcinomas nonotherwise specified (N. O. S.) and papillary carcinomas. In situ and infiltrative lobular carcinomas did not show any microcalcification. Histochemically, calcium was shown to be deposited in compound lipids. The morphology and localization of microcalcifications was similar to those described in fibrocystic disease. This should be ascribed to similar structural and cellular conditions in both diseases.

Fibrocystic disease of the breast and HLA antigens.

One hundred and ten patients with fibrocystic disease of the breast and 200 controls were HLA typed with a panel of 100 antisera for A and B locus. The main finding was the decreased frequency of BW35 antigen among patients compared to the controls. The difference remained significant in patients with the fibrous type of the disease and in patients of the nulliparous group. In addition the last group of patients showed a significant increase of All antigen.

Microcalcifications in benign breast diseases. A histological and histochemical study.

A hundred cases of fibroadenomas and 300 cases of benign breast diseases were studied without previous roentgenographic examination of the specimens. Microcalcifications were found in 19% of the fibroadenomas, in 26% of the cases of "fibrous disease" and in 57% of the cases of fibrocystic disease. Benign microcalcifications were not found in normal mammary tissue. They were steadily associated with metaplastic epithelial cells and with their abnormal secretions. Two basic types of microcalcifications were encountered: The granular microcalcifications with a predominately intracellular location and the homogeneous (with or without concentric rings) mainly associated with secreted materials. Microcalcifications were associated with metaplastic epithelial cells of the small eosinophilic variety and with their secretions, with the foam cells and with materials secreted by the apocrine cells. A common histochemical feature in cells or matrixes containing microcalcifications was the presence of compound lipids. The possible relationship of benign breast microcalcifications to the calcifications of other tissues, in connection with their association with lipids is discussed.

Mucous metaplasia of epithelial cells in fibrocystic disease of the breast. A histochemical study.

Mucous metaplasia of breast epithelium was studied by histochemical procedures in cases of fibrocystic disease. Epithelial mucins consist almost entirely of non-sulfated sialomucins. A slight amount of sulfated sialomucins was identified occasionally while neutral mucins seems to be absent. Abundant glycogen granules are contained in the cytoplasm of metaplastic cells. The secretion of sialomucins may be associated with a loss of cell antigenicity. In this case, the survival of metaplastic epithelium supports the hypothesis of the possible immunological nature of the disease.

Amount and distribution of solid and fatty tissues in the female breast and their relationship to carcinoma.

The study is based on 112 consecutive mastectomy specimens with carcinoma. Breasts were grossly divided into three basic types: solid, when showing a sizable cone of solid tissue (mammary tissue and fibrous stroma), fatty when almost completely replaced by fat, and intermediary types Ia and Ib. It appears that these types represent stages of an evolutionary process involving the anatomical structure of the breast during life. Mammary alterations gradually lead to lobular atrophy. Generalized lobular atrophy characterizes mainly fatty breasts. Lesions of fibrocystic disease are frequent in breasts of all types. In all three types of breast carcinomas were more frequently located in the outer portion of the breast. Rare locations of carcinomas are associated with the type of breast: a central location is more frequent in fatty, an inner location in intermediary and a diffuse in solid breasts. In fatty breasts irregular tumors are common while in solid breasts tumors without clear borders appear to develop. Multicentric carcinomas were much more frequent in solid breasts than in the other types of breasts. Most multicentric carcinomas are accompanied by multicentric carcinoma in situ. Infiltrative lobular and mixed (lobular-ductal) carcinomas are accompanied by lobular carcinoma in situ, lobular cancerization or both. In infiltrative ductal and the special types of carcinomas the histology of carcinoma in situ differs according to whether or not the infiltrative tumor is single or multicentric. The difference concerns the complete lack of lobular cancerization from cases with single infiltrative tumors.

Circulating autoantibodies in patients with fibrocystic disease of the breast.

Antinuclear, parietal-cell, smooth-muscle, mitochondrial, and adrenal antibodies were determined in the blood serum of 110 patients with fibrocystic disease of the breast and of 102 healthy blood donors by indirect immunofluorescence. Thirty-eight percent of the patients had detectable autoantibodies compared to 16% of the controls (P less than 0.001). Significant differences were found in the incidence of parietal-cell and smooth-muscle autoantibodies between the patients and controls. In addition, more than one autoantibody was detected in the serum of a significantly larger number of patients than controls. The findings indicate that an immunologic mechanism is involved in the pathogenesis of fibrocystic disease of the breast.

Breast masses in young girls. Report of five cases.

The pubertal breast may be the seat of lesions comparable to those of the adult female breast. Of the five girls referred to in this report, aged 11 to 15 years, three had fibrocystic disease, one had a huge intracystic papilloma and the last one had multiple papillomas. The two girls with fibrocystic disease and the one girl with multiple papillomas had a family history of breast cancer which had appeared in their grandmothers. The possible relationship between the breast diseases of the two generations is discussed.

Duct elastosis in infiltrating carcinoma of the breast.

Duct elastosis was studied in 219 patients subjected to radical mastectomy for infiltrating carcinoma of the breast, with a 10-year follow-up. Duct elastosis is a frequent finding in infiltrating breast cancer (65% of our cases). It develops in tumors of all three grades of malignancy, but it is more frequent in tumors of low grade malignancy (76% and 74% in grades I and II, respectively, and 47% in grade III tumors). In spite of their greater incidence in low malignancy tumors, the elastotic cases have a greater metastatic ratio than the non-elastotic cases (66% vs 45%). The elastotic cases also contain a significantly greater proportion of scirrhous tumors than the non-elastotic cases (86% vs. 32%). Duct elastosis and scirrhous reaction are two processes which develop in parallel, but are not related etiologically. They seem to be correlated with more advanced stages of the neoplastic disease. The influence of duct elastosis upon the ten year survival of the patients is unfavorable. this influence is not direct, and it is particularly evident in the metastatic cases. It seems to be related to the greater duration of the neoplastic disease and to the slow clinical course of tumors of low degree of malignancy.

Fibrosis as in indication of time in infiltrating breast cancer and its importance in prognosis.

The histological grading of tumours according to their intrinsic malignancy is very important in the prognosis of breast cancer but within each grade the ultimate prognosis depends mainly on the age of the tumours.We have shown that tumour fibrosis is an indication of this time factor, increasing with the age of the tumour. Within each grade the metastatic ratio is higher and the 5 year and 10 year survival less with the scirrhous than with the non-scirrhous tumours. The establishment of axillary metastases is closely connected with both the degree of malignancy and the time available, the unfavourable effect upon survival being greater in the scirrhous than in the non-scirrhous tumours.Another consequence of the passage of time, as indicated by fibrosis, is the gradual diminution of lymphoid infiltration (LI) which is mostly present in young tumours, especially those of high grades. The favourable effect of LI upon survival is demonstrated in the non-scirrhous tumours of grade III, possibly because of its great intensity, but this influence upon survival is lost as fibrosis increases and the intensity of the reaction diminishes.