title: The prognostic value of p53 and c-erb B-2 immunostaining is overrated for patients with lymph node negative breast carcinoma: a multivariate analysis of prognostic factors in 613 patients with a follow-up of 14-30 years.
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.
authors.affiliation: Department of Pathology, The Norwegian Radium Hospital, University of Oslo, Oslo, Norway.
authors.forename: W
authors.initials: W
authors.lastname: Reed
authors.forename: E
authors.initials: E
authors.lastname: Hannisdal
authors.forename: P J
authors.initials: PJ
authors.lastname: Boehler
authors.forename: S
authors.initials: S
authors.lastname: Gundersen
authors.forename: H
authors.initials: H
authors.lastname: Host
authors.forename: J
authors.initials: J
authors.lastname: Marthin
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D002277:Carcinoma / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53