The prognostic value of p53 and c-erb b-2 immunostaining is overrated for patients with lymph node negative breast carcinoma

Abstract

BACKGROUND Approximately 30% of breast carcinoma patients with negative lymph nodes die of their disease. Biologic markers such p53 protein and c‐erb B‐2 have been related to tumor progression, but their prognostic value remains controversial. METHODS Two large series of a total of 613 lymph node negative breast carcinoma patients from a single institution were analyzed with respect to tumor size, histologic grade, and immunohistochemical staining for p53, c‐erb B‐2, estrogen receptor (ER), and progesterone receptor (PgR). Interobserver variation in histologic grading was evaluated by Kappa statistics. The two series had different treatment modalities: 228 patients (SACGS group) were treated surgically with mastectomy and given 1 perioperative chemotherapy course, and 385 patients (HOST group) were treated with mastectomy and ovarian radiation and further randomized to receive postoperative treatment with radiotherapy or no adjuvant treatment. The follow‐up ranged from 14–30 years. RESULTS Immunoreactivities for p53, c‐erb B‐2, ER, and PgR did not differ significantly in the two series. p53 immunostaining was present in 187 of 613 tumors (29%), and c‐erb B‐2 immunoreactivity was present in 58 of the tumors (10%). Three hundred forty‐eight tumors (57%) were positive for ER. Kappa statistics value of interobserver variation in the histologic grading of ductal carcinomas was 0.69, which is considered to be a substantial degree of agreement. No significant differences in survival were found when comparing p53, c‐erb B‐2, ER, and PgR positive and negative cases. However, both recurrence free survival rates and overall survival rates after 10 years were significantly better in the T1N0M0 group compared with the T2N0M0 group (81% vs. 67% [P < 0.0001] and 85% vs. 70% [P < 0.0001]). Ten‐year recurrence free survival rates for patients with histologic Grade 1 versus Grades 2–3 (according to Elston and Ellis' modification of the Bloom and Richardson method) tumors were 90% and 70%, respectively (P < 0.0001), and overall survival rates for the same groups were 94% and 81%, respectively (P=0.0002). After 30 years of follow‐up, the overall survival rate for patients with tumors of histologic Grade 1 versus Grades 2–3 were 87% and 68%, respectively, and were 78% and 66%, respectively, for patients with tumors ≤ 2 mm versus those with tumors > 20–50 mm. Approximately 35% of the patients with tumors of histologic Grades 2–3 and measuring > 20 mm were dead after 10 years of follow‐up, contrary to 6% of the patients with tumors of histologic Grade 1 measuring ≤ 20 mm. A significantly more favorable prognosis also was observed in patients in the HOST group treated with adjuvant radiotherapy. CONCLUSIONS Histologic grade and tumor size were found to be major prognostic factors for patients after 30 years of follow‐up. c‐erb B‐2 and p53 immunostaining does not appear have any independent prognostic value. Adjuvant radiotherapy may be of value in the treatment of patients with localized tumors. Cancer 2000;88:804–13. © 2000 Am...

Expression of c-erbB-2 and p53 in Breast Carcinoma Patients: Comparison with Traditional Prognostic Factors and Survival

“…In contrast, other studies demonstrated no effect of c-erbB-2 on prognosis. 22,23 We observed c-erbB-2 positivity in a high percentage (53%) of patients, and an association with early relapse and DFS was found on univariate analysis. However, c-erbB-2 was not an independent prognostic factor for disease Expression of c-erbB-2 and p53 in breast carcinoma patients relapse and DFS in either all patients or ALNnegative patients.…”

Methylation-dependent silencing of CST6 in primary human breast tumors and metastatic lesions

“…Numerous molecular markers have been examined for their predictive value in breast cancer prognostication, but histopathologic grade emerges as the most important indicator of longterm patient outcome (Simpson et al, 2005;Symmans, 2005). However, histopathologic grade generally correlates with the expression of genes associated with increased cell proliferation p53), growth (HER-2), and invasiveness (matrix metalloproteinases) (Mirza et al, 2002;Reed et al, 2000). In contrast, low-grade breast tumors express genes associated with low cellular proliferation (p27) and differentiation (ER and PR) (Lau et al, 2001;Symmans, 2005).…”

Expressão imuno-histoquímica de c-erb-B2 e p53 em carcinomas gástricos

“…Esse acúmulo pode ser detectado através do método de imuno-histoquímica (10,21) . Mutações no gene p53 foram observadas numa variedade de carcinomas, como nos colorretais (44) , mamários (33) , esofágicos (13) e gástricos (12,22,36) . Em carcinomas gástricos, a freqüência de mutações do p53 varia de 4% a 64%, dependendo principalmente do tipo de técnica utilizada para a detecção.…”