Immunohistochemical expression of the c-kit proto-oncogene product in human malignant and non-malignant breast tissues.

X Chui,J Yamashita,M Ogawa,H Egami,T Kurizaki,H Ohmachi,S Yamamoto

doi:10.1038/bjc.1996.236

Abstract

The immunohistochemical expression of c-kit proto-oncogene product in 57 breast cancer tissues was studied using anti-c-kit proto-oncogene product antibody in comparison with 20 normal breast tissues and 58 benign breast tumours. In normal breast tissues, the c-kit proto-oncogene product was strongly expressed on cell membrane and/or cytoplasm of alveolar and ductal cells. The immunoreactive score (IRS) of c-kit proto-oncogene product in normal mammary epithelia was 6.22 +/- 2.11 (mean +/- s.d.). In benign breast diseases, the c-kit proto-oncogene product was detected heterogeneously with a reduced IRS (3.33 +/- 2.44). In breast cancer tissues, the expression of the immunoreactive c-kit proto-oncogene product was often deleted and the average IRS was significantly reduced compared to those of normal breast tissues or benign breast diseases tissues. Among benign diseases, the average IRS of intraductal papilloma was significantly reduced (1.34 +/- 1.70) and the staining intensity and pattern were found to be similar to those seen in breast cancer. The results in this study suggested that the c-kit proto-oncogene product is correlated with the growth control or the differentiation of normal breast epithelium. Also, the loss of the expression of this protein may indicate the change of the signal transduction in relation to malignant transformation in human mammary epithelium.

Highlights

The immunoreactive expression of c-kit proto-oncogene product was not observed in human normal lung or seminal vesicles tissue (Natali et al, 1992a; Matsuda et al, 1993), whereas it was found in 56% of SCLC (Matsuda et al, 1993 and 80% of seminomas (Strohmeyer et al, 1991)
It was expressed heterogeneously in benign breast disease and the deletion was observed in breast cancer specimens with high incidence suggesting that the reduced c-kit protooncogene product expression is a general phenomenon in breast cancer
The high expression of the c-kit protooncogene product in normal breast tissue indicated that this protein may be related to the regulation of the proliferation and/or the differentiation of human normal mammary epithelia through the c-kit signalling pathway

Summary

Methods

Fifty-seven patients with primary breast cancer and 58 patients with benign breast disease were studied. All patients were female and the ages of patients with breast cancer and benign disease ranged from 29 to 73 years (average age 51.8 years) and from 22- 89 years (average age 43.7 years) respectively. Normal breast tissues were obtained from 20 surgical specimens of mastectomised patients. Tissues were fixed in 10% buffered formalin and embedded in paraffin. One serial section from each tissue sample was stained with haematoxylin and eosin for routine histological examination and others were treated for Correspondence: M Ogawa Received 3 March 1995; revised 26 September 1995; accepted 19 October 1995 demonstration of the c-kit proto-oncogene product, as described below

Results

Discussion

Conclusion