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Background. Cathepsin D is an estrogen-regulated lysosomal protease that may be overexpressed in breast cancer. Several studies based on biochemical analysis of tumor cytosol have shown that high levels of cathepsin D are associated with poor outcome in patients with breast cancer. In contrast, a few immunohistochemical studies have shown that cathepsin D positivity in breast cancer cells indicates a favorable prognostic outcome or is of no prognostic significance. Methods. Because of the current controversy, the authors studied, using immunohistochemistry, the distribution (0 to 3) and intensity (0 to 3) of cathepsin D in Stage I and II infiltrating ductal carcinoma of the breast from 245 patients treated at the City of Hope National Medical Center, Duarte, California, from 1970 to 1986. A commercially available rabbit antiserum to purified human cathepsin D and the standard avidin-biotin complex method were used. Statistical analysis was based on a combined low (0 or 2) or high (3 to 6) score. Results. A high cathepsin D score was associated with Stage II disease (P = 0.007), positive lymph nodes (P = 0.019), high nuclear grade (P = 0.005), and c-erbB-2 oncogene amplification (P = 0.013). Cathepsin D positivity was not an independent prognostic indicator of disease-free survival (DFS) or overall survival (OS). In a subgroup analysis, the presence of cathepsin D had only a modest association with predicting a shorter DFS in patients with negative lymph nodes (P = 0.072) or positive progesterone receptors (PR) (P = 0.086). Conclusions. Immunohistochemical analysis of cathepsin D, with the antiserum used in this study, is not an independent predictor of outcome in patients with breast cancer because of its strong associations with several well-established prognostic indicators. Cancer 1993; 71:2756-63.

Hector Battifora, M.D.,* Hans R. Soresen, M.D., [unkeyable] Parula Mehta, H.T.,* Chul Ahn, Ph.D.,* Joyce Niland, Ph.D.,* Esther Hage, M.D., [unkeyable] David E. Pettijohn, Ph.D., [unkeyable] and Lennart Olsson, M.D. Section Background. Squamous cell lung carcinoma (SLC), the most frequent type of lung cancer, generally is treated surgically and its prognosis is poor. The only current clinically useful prognostic criterion is lymph node staging (TNM classification). Expression of a novel tumor-associated carbohydrate epitope Gal[unkeyable]1-3[Fuc[unkeyable]1-4] GlcNAc[unkeyable]1-4[Fuc[unkeyable]1-3]GlcNAc[unkeyable]1-3Gal[unkeyable]1 -4Glc identified by the 43-9F monoclonal antibody (MoAb) is associated with the growth pattern of SLC cell lines in athymic mice and in vitro. This implies that the 43-9F eoitope may be related to tumor progession in patients with SLC and that, as such, it could be of prognostic value. Methods. Primary tumor specimens from 231 patients with lung carcinoma (130 with SLC, 64 with adenocarcinoma, 10 with small cell carcinoma, 16 with large cell carcinoma, and 11 with adenosquamous carcinoma) were examined by immunohistochemical studies on formalin-fixed, paraffin-embedded tissue samples for immunoreactivity with an MoAb to the 43-9F antigen. Univariate and step-wise Cox regression analyses were used to compare survival time by histopathologic diagnosis, smoker status, TNM classification, and type of surgical treatment. Results and Conclusions. Patients with 43-9F epitope-positive SLC tumors had a significantly (P < 0.01) better prognosis than patients with epitope- negative tumors. In contrast, no association was seen between 43-9F epitope expression and survival time for patients with lung adenocarcinomas. Further, the prognostic value of 43-9F expression in SLC was found to be superior to the N-classification with the added advantage that it requires access only to primary tumor tissue and thus is available before therapy. Cancer 1992; 70:1867-1872.

The p53 tumor suppressor gene has been implicated in apoptotic cell death. The present study was conducted to investigate whether expression of p53 protein is increased in association with kainic acid-induced neuronal apoptosis. Adult male Sprague-Dawley rats were treated systemically with the glutamate analog kainic acid, and sacrificed either 4 or 30 h after the onset of seizure activity. Immunohistochemistry was performed on paraffin-embedded sections using an anti-p53 polyclonal antibody. At both time points, increased p53 immuno-reactivity was observed predominantly in the nucleus of apoptotic neurons. These findings lend additional support to the hypothesis that p53 is a marker of neuronal apoptosis in the CNS, and suggest that nuclear accumulation of p53 protein may be an important mediator of neuronal death.