Transforming growth factor-beta1 and tumor growth factor-beta-inducible gene-H3 in nonrenal transplant cyclosporine nephropathy.

Cyclosporine nephropathy (CyAN) is a major limiting factor in the otherwise successful widespread use of cyclosporine in solid organ transplant. Transforming growth factor-beta1 (TGF-beta1) has been implicated as an important fibrogenic cytokine in the development of this disease. TGF-beta-inducible gene-H3 (beta(ig)-H3) is a TGF-beta1- induced gene product, which acts as a marker for biologically active TGF-beta1. This study reports TGF-beta1 gene expression and beta(ig)-H3 tissue distribution in non-renal allograft CyAN. Renal tissue from nine patients who had developed CyAN after successful heart or heart-lung transplantation and from four kidneys removed for tumour were analyzed for TGF-beta1 gene expression beta(ig)-H3 protein with reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry, respectively. TGF-beta1 gene expression was increased in CyAN compared to nephrectomy (P<0.0001). Beta(ig)-H3 protein expression was identified in distal convoluted tubular epithelium and parietal glomerular epithelium in CyAN, and not in nephrectomy samples. Expression of TGF-beta1 mRNA was significantly higher in renal tissue from patients not receiving angiotensin converting enzyme inhibitor (ACEI) therapy for hypertension (P<0.05). These findings support the hypothesis that TGF-beta1 is an important cytokine in the development of CyAN, independent of its role in chronic rejection in renal allografts.

Tumour grade does not change between primary and recurrent mammary carcinoma.

The primary tumour grade in 115 patients with infiltrating ductal carcinoma of the breast was compared with the type of the ductal carcinoma in situ (DCIS) component and with the grade of 169 locally recurrent and metastatic lesions. 102 patients had axillary lymph node metastases at the time of primary surgery, 49 had subsequent recurrences and 36 had both. There was concordance of grade between the primary tumour and axillary lymph node metastases and with subsequent locally recurrent and metastatic lesions. The type of the DCIS component was also significantly associated with the grade of the infiltrating component. No evidence of progression of tumour grade between these phases of mammary carcinoma was found.

Histopathology of breast cancer in relation to age.

Histological reports of 1869 consecutive women with invasive breast cancer have been reviewed to determine whether histological features of the tumour's were related to the patients' age. The patients, treated between 1983 and 1992, were divided into four groups, based on age. There were 148 aged < or = 39 years, 355 aged 40-49 years, 984 aged 50-69 years and 382 aged 70 years or more. The most outstanding finding was the increase in incidence of grade III infiltrating ductal carcinoma in those aged < or = 39 years (P < 0.0001). Certain tumour types, in particular lobular, were reported more frequently in the oldest age group. Additionally, there was a significant reduction of axillary lymph node metastases, vascular invasion and lymphoplasmacytic stromal reaction with increasing age, all of which were independent of tumour grade. These data suggest that there may be age-related changes in the histology of breast cancer and, in some cases, less aggressive features in the elderly. However, as the life expectancy of women over the age of 70 may be many years, treatment should be based on histological prognostic features of the primary tumour rather than age alone.