Expression of Bcl-2 protein in human primary breast carcinomas and its correlation with multifocality, histopathological types and prognosis.

The Bcl-2 gene product prevents programmed cell death (apoptosis) and possibly promotes tumour development. This protein has mainly been demonstrated in the cytoplasm of various normal and neoplastic cells, including normal mammary epithelia and breast carcinomas. The aim of this retrospective study was to correlate the immunohistochemical expression of Bcl-2 protein with the multi-unifocality and the histology of the two main types of breast carcinoma. We used monoclonal antibody 124 to investigate Bcl-2 expression in paraffin sections of 62 primary breast carcinomas. Bcl-2 expression was associated mainly with this lobular carcinoma. High Bcl-2 protein positivity was found in this type, and was statistically significant in comparison to the level of Bcl-2 in ductal, NOS carcinomas (lobular versus ductal, NOS, P < 0.0001). In the entire group, including all histological types, Bcl-2 expression was higher in multifocal tumours (P = 0.005). Statistical significance (P < 0.03) was also found within the group of ductal, NOS cases, showing that Bcl-2 protein expression is associated with multifocality, irrespective of the histology of breast carcinomas. No definite association between Bcl-2 expression and prognosis was found. Our results suggest that Bcl-2 protein plays some role in the development of multifocality in breast carcinomas.

Undifferentiated carcinoma of the parotid gland in a white patient: detection of Epstein-Barr virus by in situ hybridization.

Paraffin sections of an undifferentiated salivary gland carcinoma of lymphoepithelioma type, arising in a white (Greek) patient and confirmed by immunohistochemistry, were examined for the presence of Epstein-Barr virus (EBV), using in situ hybridization to detect EBV-specific EBER1 message. Epstein-Barr virus was detected in malignant epithelial cells, but was not found in lymphoid stroma or in residual benign salivary epithelium. These results confirm the existence of an association between EBV and tumor cells of undifferentiated carcinoma of parotid gland. This is the first demonstration of EBV in a salivary gland lymphoepithelioma arising in a non-Eskimo, white patient. This finding suggests that the association of EBV with undifferentiated salivary gland carcinoma may exist in geographic regions remote from Greenland.

Phenotype of Hodgkin and Sternberg-Reed cells and expression of CD57 (LEU7) antigen.

Possible associations between the immunophenotype of Hodgkin (H) and Sternberg-Reed (S-R) cells, the expression of CD57 (Leu 7) antigen, and the presence of Epstein-Barr virus (EBV) were investigated in lymph node specimens from 50 cases of Hodgkin's disease (HD), including 26 cases of mixed cellularity and 24 cases of nodular sclerosis. Tissues were fixed in 10% neutral formalin, or/and B5 solution. H and S-R cells were CD30+, CD15+ (85% of the cases) and LCA (CD45). A proportion of neoplastic cells positive for either T-cell markers (CD3) or B-cell markers (CD20) was observed in 10% and 34% of the cases, respectively. Membrane positivity for CD57 antigen was found in H and S-R cells in 10 cases (8 cases of mixed cellularity, and 2 cases of nodular sclerosis). Such immunopositivity was only observed in B5-fixed sections. No staining for CD57 antigen was identified in H and S-R cells of any case with CD20 positive neoplastic cells. H and S-R cells of both CD57-positive and CD57-negative cases were further studied by immunohistochemistry for LMP1, by in-situ hybridization for EBER and by polymerase chain reaction (PCR) for EBV-DNA. No association was identified between the expression of CD57 antigen and the presence of EBV sequences, transcripts or proteins. Our findings do not support a B-cell origin for H and S-R cells in CD57-positive cases of Hodgkin's disease and suggest that these neoplastic cells may be related to natural killer (NK) or T-cells expressing CD57 antigen.

Immunohistochemical detection of the c-myc oncogene product in normal, hyperplastic and carcinomatous endometrium.

The expression and the distribution of the c-myc oncogene product (p62) was studied by a 3-step immunoperoxidase technique using the monoclonal antibody myc 1-6 E10 in 22 cases of normal endometrium (11 proliferative and 11 secretory phase), 43 endometrial hyperplasias (24 adenomatous and 19 adenocystic) and 26 endometrial carcinomas. Increased expression of c-myc product appeared in endometrial carcinomas compared with respective non-neoplastic tissue (p < 0.001). The immunolocalization of the c-myc protein shows a consistent difference between the various histologic patterns of non-neoplastic and neoplastic endometrium. Nuclear staining of the c-myc product was demonstrated in epithelial cells of the proliferative phase and predominantly in poorly differentiated forms of endometrial carcinomas. On the other hand cytoplasmic staining was found predominantly in the secretory phase and in well differentiated carcinomatous endometrium. In hyperplastic endometrium an intermediate immunohistochemical pattern was observed. The results of the present study emphasize that c-myc product overexpression and localization plays an important role in initiation, differentiation and progression of endometrial carcinomas.

Langerhans cells and lymphocyte subsets in human gastrointestinal carcinomas. An immunohistological study on frozen sections.

In an immunohistochemical study of 38 human gastric and 40 human colonic carcinomas Langerhans cells, suppressor and helper lymphocytes were identified on frozen sections by using anti-CD1, anti-CD8 and anti-CD4 monoclonal antibodies. Tumours were divided into those with few (< 3 per high power field) and those with many (> 3 per high power field) Langerhans cells as well as into those with high number of CD4 and CD8 cells (> 30 per high power field). No significant difference in the number of Langerhans cells regarding histologic types, degree of differentiation and metastatic/non-metastatic groups of either gastric or colonic carcinomas was found. On the contrary the numbers of Langerhans cells related significantly (p < 0.05) to density of T-cell and especially CD4 cell infiltrations of gastric and colonic carcinomas. This finding supports the role of Langerhans cells as antigen presenting cells and their involvement in T-cell activation against neoplastic cells of human gastrointestinal carcinomas.

Sjögren's syndrome in progressive systemic sclerosis.

Forty-four sequential, unselected patients with progressive systemic sclerosis (PSS) were prospectively evaluated for evidence of coexistent Sjögren's syndrome (SS). This diagnosis was established when a patient with focal lymphocytic infiltration in the labial salivary gland (LSG) biopsy, scoring greater than or equal to 2+ in Tarpley's scale, had keratoconjunctivitis sicca (KCS) (positive rose bengal test) and/or xerostomia (subjective xerostomia and decreased parotid flow rate). Ten patients had an LSG biopsy score of greater than or equal to 2+, 3 a 1+ score, 17 had mild to moderate fibrosis only and 14 had normal tissue. Nine of the 10 patients with a greater than or equal to 2+ score had SS, according to applied criteria, suggesting a 20.5% prevalence of SS in our population with PSS. On the other hand, pure fibrosis in the biopsy was felt to be secondary to PSS. Parotid gland enlargement was present in 44.4% of the patients with SS, but was extremely uncommon in the fibrosis and normal tissue groups. Subjective xerophthalmia and xerostomia, although elicited by specific questionnaire in the majority of the patients with SS, did not constitute major complaints. Serious internal manifestations, with the exception of esophageal and pulmonary involvement, were unusual in all groups. Anti-Ro (SSA) antibodies were detected in 33.3% of the patients with SS and 11.8% of those with fibrosis. Our study suggests that SS in scleroderma is relatively common and, although lacking prominent exocrine gland symptomatology, resembles primary SS in some clinical and serologic respects.

Prevalence of primary Sjögren's syndrome in an elderly population.

Sixty-two elderly apparently healthy volunteers, inmates of a public nursing home, were examined for evidence of primary Sjögren's syndrome (pSS). Evaluation included a specific questionnaire for subjective xerophthalmia and xerostomia, slit-lamp eye examination after rose Bengal staining. Schirmer's I test, stimulated parotid flow measurement, testing of sera for autoantibodies and labial minor salivary gland biopsy. A greater than or equal to 2+ lip biopsy score on Tarpley's scale was a sine qua non for the diagnosis of Sjögren's syndrome. Labial salivary gland (LSG) biopsy revealed fibrosis and/or fatty infiltration in the majority of the individuals, related to ageing. However, four people had a lip biopsy score of greater than or equal to 2+, which, supplemented by other objective criteria, classified three of them as having pSS. Another four had an LSG biopsy score of 1+, and although they fulfilled other objective criteria, they could not be characterized as pSS. All these individuals were completely asymptomatic, and none of them had anti-Ro(SSA) or anti-La(SSB) autoantibodies. The present study suggests that pSS in elderly people in elderly people is subclinical, benign and relatively common.

Cyclosporin A (CyA) in primary Sjögren's syndrome: a double blind study.

The efficacy and toxicity of cyclosporin A (CyA) were studied in a blind fashion in 20 patients with primary Sjögren's syndrome (pSS). The dose of CyA or placebo was 5 mg/kg of body weight daily. Among the 20 patients, 10 received CyA and 10 placebo. The two groups were matched for age, sex, and disease duration. Patients treated with CyA improved in subjective xerostomia in comparison with patients treated with placebo. Subjective xerophthalmia and recurrent parotid gland enlargement did not differ in the two groups. No change in Schirmer's test and stimulated parotid flow rate was observed in either group. In contrast, the histopathological lesion of patients treated with CyA remained unchanged in most of the patients, while in the placebo treated group the lesion deteriorated. Laboratory parameters did not change before or after treatment in either group. The only clinical side effect observed in the CyA treated group was hypertrichosis.