Association of immunohistochemical p53 tumor suppressor gene protein overexpression with prognosis in highly proliferative human mammary adenocarcinomas

• Published in: World journal of surgery 1994-11, Vol.18 (6), p.827-832
• Main Authors: Schimmelpenning, Hendrik, Eriksson, Elina T., Zetterberg, Anders, Auer, Gert U.
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - chemistry; Adenocarcinoma - mortality; Breast Neoplasms - chemistry; Breast Neoplasms - mortality; Female; Humans; Immunohistochemistry; Immunoreactive Tumor Cell; Prognosis; Proliferate Cell Nuclear Antigen; Proliferate Cell Nuclear Antigen Expression; Proliferating Cell Nuclear Antigen - analysis; Protein Proliferate Cell Nuclear Antigen; Tumor Suppressor Gene Expression; Tumor Suppressor Protein p53 - analysis
• ISSN: 0364-2313; 1432-2323
• DOI: 10.1007/BF00299077

An increasing body of evidence suggests that in addition to conventional histopathologic tumor characteristics, DNA content measurements, cell kinetic data, and investigatios of tumor suppressor gene expressions might be of valuable information in breast cancer patients. Against this background we investigated immunohistochemically overexpression of the interphase associated protein proliferating cell nuclear antigen (PCNA) and the mutant p53 protein in routinely paraffin‐embedded surgical specimens from 180 breast cancer patients with known nuclear DNA profiles. The mean clinical follow‐up was 16 years (range 13–20 years). The percentage of PCNA immunoreactive tumor cell nuclei ranged between 20%) and p53 protein overexpression (p=0.019). Mutant p53 protein overexpression was found in 44 of 180 (24%) cases and was significantly related to high histologic tumor grade (p=0.004), DNA aneuploidy (p=0.001), and high levels of PCNA expression (p=0.001). Patients with highly proliferative carcinomas (>20% PCNA expression) had a shortened distant metastases‐free survival when their neoplasms overexpressed p53. In contrast, the distant metastases‐free survival of patients with highly proliferative, p53‐negative tumors was significantly longer (p=0.03). Immunohistochemical p53 protein overexpression thus appears to be indicative of an increased malignant potential in breast cancer patients. Highly proliferative tumors composed of p53 immunoreactive neoplastic cells clinically seem to behave more aggressively than the highly proliferative p53‐negative tumors. Résumé En plus des caractéristiques tumorales histopathologiques classiques, y compris le contenu en ADN, la cinétique cellulaire et l'étude de l'expression de gènes suppresseurs sont peut‐être importantes dans le bilan d'un cancer du sein. Nous avons examiné par des coupes en paraffine la surexpression immunohistologique de la protéine associée avec l'interphase (le proliferating cell nuclear antigen: PCNA) et la mutante p 53 chez 180 femmes atteintes de cancer de sein ayant des caractéristiques d'ADN connus. Le pourcentage de PCNA immunoréactif variait entre