Breast-sparing therapy of breast cancer: on the combination of radiation therapy with adjuvant chemotherapy

From January, 1975 through June, 1986, 426 patients with mammary carcinomas were submitted to primary, breast-preserving therapy at the Gynecological Hospital of the University of Heidelberg. 212 women with a minimum observation time of twelve months fulfilled the criteria of a "typical" treatment: tumor size up to 3 cm, segment/quadrant resection and axillary lymphonodectomy with at least eight lymph nodes removed, radiotherapy of the residual breast with greater than or equal to 45 Gy, in case of histological lymph node manifestation adjuvant hormonal and/or chemotherapy. The average observation time was 38 months, the medium age 48 years. Patients with histological lymph node manifestations were compared with a matched control group of women treated treated by modified radical therapy. According to the error estimation of Kaplan and Meier (1958), no differences were found for local recurrence rate, disease-free survival, and overall survival. Patients treated by organ-preserving therapy with adjuvant chemotherapy were opposed to a matched control group of women treated only by surgical/radiological, organ-preserving therapy. In patients with chemotherapy, the incidence of cutaneous erythema (29% versus 24%), telangiectasia (34% versus 24%), hyperpigmentation (41% versus 34%) showed an upward tendency, but was not significantly increased. There was no difference in the incidence of clinically palpable fibroses (37% versus 42%) and fibroses shown by mammography (54% versus 51%). The frequency of pneumonitis/fibrosis of the retromammary lung area (22% versus 10%) after chemotherapy was two times higher than in the matched control group not treated by chemotherapy.     

HLA haplotype study of 53 juvenile insulin-dependent diabetic (I.D.D.) families

Fifty-three families with at least one IDD patient were genotyped for 5 markers of the HLA complex including Bf and DR. In 8 families one of the parents was also affected and in 12 families more than two children were diseased. In total, 76 patients were genotyped. Their haplotypes were compared with those of 106 unrelated controls (the parents of 53 genotyped families).

• 1) 

  Three haplotypes or segments of them (A2, Cw3, B15, BfS, DR4; Aw30, Cw5, B18, BfF I, DR3; and Al, Cw7, B8, BfS, DR3) were found more frequently in IDD patients.
• 2) 

  Measured by the 6 formula, the association of the postulated IDD susceptibility gene was very strong with the D-end of two of these haplotypes: BfF1, DR3 and BfS, DR4. However, the association was weak with the DR3 of the haplotype Al, Cw7, B8, BfS, DR3.
• 3) 

  An excess of HLA-identical affected siblings was found.
• 4) 

  An excess of DR3/DR4 heterozygotes was observed. By contrast, the observed frequency of patients homozygous for DR3 or DR4 was not increased, but even slightly decreased.

The data support a model of inheritance comprising at least two closely linked specifically "diabetic" loci (most of the time marked by B18, BfFl, DR3 and B15, BfS, DR4) and a non-specifically "diabetic" haplotype favouring auto-immunisation (most of the time marked by B8, BfS, DR3). This model is discussed in the light of the presented data and of those of the literature.     

Possible Relation of p53 and mdm-2 Oncoprotein Expression in Thyroid Carcinoma: A Molecular-Pathological and Immunohistochemical Study on Paraffin-Embedded Tissue

Routinely processed tissues from a series of benign and malignant thyroid lesions were immunohistochemically investigated with antibodies against p53 and mdm-2. p53 was immunolocalized in <10% of nuclei in 2/80 nodular goiters, 2/60 follicular adenomas, 26/68 follicular carcinomas, 7/40 papillary carcinomas, 3/10 “insular” carcinomas, and 10/31 anaplastic carcinomas. More than 10% positively stained nuclei were found in 2 widely invasive follicular, 2 insular, and 15 anaplastic carcinomas. All p53-positive cases showed a concomitant immunohistochemical mdm-2 expression; an immunohistochemical colocalization on serial section was demonstrated in 12 anaplastic carcinomas. Screening by polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) analysis of these 12 cases revealed no relevant mutations in the coding regions of exons 2–11 of the p53 gene. Additionally, 1 follicular adenoma, 6 follicular carcinomas (4 minimally and 2 widely invasive), 1 papillary, and 2 poorly differentiated insular carcinomas were mdm-2 positive without immunohistochemically detectable p53 expression. These results provide evidence that wild-type p53 expression in thyroid carcinomas may be associated with mdm-2 induced formation of stable complexes. However, the role of p53 mutations and p53 protein inactivation owing to other factors (e.g., mdm-2) in the progression of thyroid carcinomas is still poorly understood.     

Genetic similarity of Candida albicans strains from vaginitis patients and their partners.

The moderately repetitive sequence Ca3 was used to fingerprint strains of Candida albicans isolated from vulvovaginal infections of 10 women and strains isolated from their male partners. The Dendron software package was then used to compare the DNA fingerprints of these strains with those of vaginal commensals from women from the same geographical locale, vaginal commensals from women from a different geographical locale, and commensals from male partners of asymptomatic women from the same geographical locale. The results demonstrate that, in the majority of cases (8 of 10), strains from symptomatic patients and their partners are either identical or more similar to each other than to other strains, infecting strains do not represent a group genetically distinguishable from vaginal commensal isolates from women from the same geographical locale, and both infecting strains and commensals from individuals in the test locale can be distinguished from commensals obtained in another geographical locale. The results also suggest that women with vaginal infections are responsible for strain replacement in their male partners.     

A comparative study of the expression of cytotoxic proteins in allergic contact dermatitis and psoriasis: spongiotic skin lesions in allergic contact dermatitis are highly infiltrated by T cells expressing perforin and granzyme B

Recent reports indicate that cytotoxic T cells are critically involved in contact hypersensitivity reactions in animals. In this study we sought to investigate the in vivo expression of cytotoxic granule proteins in the elicitation phase of allergic contact dermatitis in humans. Skin biopsy specimens were obtained from patients with allergic contact dermatitis (n = 8) and psoriasis (n = 6) and from controls with normal skin (n = 6). Expression of perforin and granzyme B was investigated by in situ hybridization and immunohistochemistry. In contrast to normal skin and psoriasis, a significant enhancement of perforin and granzyme B gene expression and immunoreactivity was observed in the mononuclear cell infiltrate of allergic contact dermatitis. Immunoreactivity for perforin and granzyme B was mainly found in the cytoplasm of lymphocytic cells, which were located in the dense perivascular infiltrate as well as at sites of marked spongiosis in the epidermis. Double immunostaining revealed that both CD4+ and CD8+ T cells are capable of expressing perforin and granzyme B. In conclusion, our data suggest that T-cell-mediated mechanisms involving cytotoxic granule proteins may elicit epidermal cell injury in vivo and thereby strongly contribute to the development of allergic contact dermatitis in humans.     

The presence of immunosuppressive ''p15E-like'' factors in the serum and urine of patients suffering from malign and benign breast tumours.

Autoantibodies in sera from patients with systemic lupus erythematosus (SLE) and onchocerciasis recognize calreticulin (CaR), a calcium-binding protein, as antigen. In this study we present the immunological properties of two synthetic peptides prepared to correspond to the 1-24 and 7-24 amino acid sequence of CaR. In contrast to information previously reported for the recombinant protein, the CaR-peptide analogues appeared immunoreactive to anti-Ro/SSA autoimmune sera. Human sera from patients with SLE, Sjögren's syndrome (SS), rheumatoid arthritis (RA), as well as mixed connective tissue disease (MCTD), demonstrated a positive autoimmune response (binding of antibodies), to the CaR-peptide analogues. These findings suggest that anti-calreticulin autoantibodies are not restricted to any disease specificity.     

HLA-DR2 in two sibships with insulin-dependent diabetes mellitus.

We report two families selected from 124 genotyped Caucasian insulin-dependent diabetes mellitus (IDDM) families because of unusual features. In both families, all offspring are affected and four out of six bear the allele HLA-DR2 which is an uncommon phenotype among diabetic patients. Onset before the age of 1 year in all the patients of one family, association with optic atrophy in the other, and the existence of pairs of affected sibs of different HLA types in both, are infrequent findings and support the evidence of heterogeneity in IDDM.     

Alveolar bone loss in rats after immunization with Actinomyces viscosus.

We investigated a possible cause-and-effect relationship between sensitization against Actinomyces viscosus Nyl and destructive periodontal disease in RIC-Sprague-Dawley rats. Germfree rats (66) were either immunized with A. viscosus Nyl (day 20) or orally infected with A. viscosus Nyl (days 38 and 39) or both. We measured alveolar bone loss in maxillary and mandibular molars, in vitro T-lymphocyte responsiveness, and serum antibody titers. In immunized and monoassociated rats bone loss in both jaws progressed rapidly between days 37 and 72, whereas the rate of further resorption decreased until day 100. In monoassociated rats, development of bone loss was much slower, and the maximum resorption measured was, at best, half of the bone loss compared with the former group. However, no amplification of bone loss by immunization was observed in a second experiment using 63 conventional rats kept in relative gnotobiosis. Antibody titers to A. viscosus Nyl in gnotobiotic monoassociated rats were higher in immunized animals, whereas no difference was found in the respective groups of the relative gnotobiotic experiment. The fact that immunization more than doubled alveolar bone loss in gnotobiotic monoassociated rats confirms the allergic nature of the disease. The lack of such an effect under conventional conditions points to suppressor mechanisms whose decrease might convert stable periodontal lesions into progressive ones.