Clinical Correlation of HER-2/neu Overexpression in Patients with Breast Cancer Sung Yong Kim, Tae Yoon Kim, Jae Jun Kim, Chang Ho Kim, Ok Pyung Song, Min Hyuk Lee, Eui Han Kim 1, and Moo Sik Cho Departments of Surgery and 1 Pathology, College of Medicine, Soonchunhyang University, Cheonan Hospital, Cheonan, Korea Purpose: Breast cancer is a common malignant tumor for Korean women. Various oncogenes have been demonstrated in malignant tumor cells. There were many reports on the relationship between the prognosis and the tumor markers, and particularly for HER-2/neu; however, this relationship is controversial. The aim of this study was to perform immunohistochemical staining for the HER-2/neu antigenic protein in breast cancer patients to evaluate the expression rate of this antigenic protein, and to compare the correlations with the patients' prognosis. Methods: The medical records of 100 patients who were diagnosed with breast cancer and who were treated with mastectomy between January 1996 and December 1999 at Soonchunhyang University Cheonan Hospital were selected according to the tissue condition of the paraffin block fixations. The prognostic factors were then investigated. The immunohistochemical expression of HER-2/neu was examined and compared with the survival rate using a Kaplan-Meier estimate and a log rank test. Results: One hundred patients were included in this study, had a mean (SD) age of 47.9 (plus or minus 10.5) years and a follow-up duration of 59.9 (plus or minus 13.3) moths The overall mortality was 35% (35/100) and the mean survival time (SD) was 64.4 (plus or minus 12.0) months. The overall 5-year survival rate was 77.0%. Among the study variables, the tumor stage was a significant predictor of survival, and it as associate with a significantly low survival rate for stage III tumor. Lymph node metastasis, hormonal receptor status, histologic grade and HER-2/neu overexpression were significantly associated with the survival rate for patients with breast cancer. Conclusion: HER-2/neu is a very useful prognostic factor, and statistical significance was achieved for this factor. (Journal of Korean Breast Cancer Society 2004;7:244-250) Key Words: Breast cancer, Prognostic factor, HER-2/neu :,, HER-2/neu
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246 한국유방암학회지 제 7 권 제 4 호 2004 ꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏ 0 1+ 2+ 3+ Fig. 1. HER-2/neu Immunohistochemical Staining ( 400). 후 고배율 시야에서 염색된 종양 세포수 및 염색강도를 4 개의 등급(- +++)으로 표시하였으며, 염색이 안 되 거나(-) 염색의 강도가 낮은(+)군을 음성군으로 염색의 강도가 높은(++, +++)군을 양성군으로 설정하였다 (Fig. 1). 결 과 1) 대상 환자의 전반적 특성 대상 환자를 유형별로 보면 침윤성 유관암 88예, Paget 씨 병이 4예, 유두상암 4예, 수질성암이 4예였다. 이들의 평균연령은 47.9세였고, 40대에서 호발연령이었으며, 암의 발생부위는 우측 예가 52예 그리고 좌측 예가 48예로 이 를 세분하면 상외측이 55예로 가장 높은 비율을 차지하였 다. 유방암을 Elston-Ellis modification of Scarff-Bloom-Richardson grading system(6)에 의한 조직 등급(Histologic grade)에 따라 분류하면 I등급이 34예, II등급이 45예 그리 고 III등급이 21예였다. 유방암 중 유방절제술에 의해 림 프절 전이여부가 확인된 예는 52예였으며, 2002년 발표된 AJCC 암 병기 분류(7)에 의한 암 병기는 I기가 13예, II기 가 47예, 3기가 40예였다(Table 2). 유방암조직에서 HER-2/neu는 면역효소에 의한 염색에 서 종양조직의 세포막과 세포질에 염색되었으며 발현이 안 되거나 염색의 강도가 낮았던 음성군의 경우가 53예, 발현율이 높았던 양성군의 경우가 47예였고, 호르몬 수용 체(Estrogen receptor)양성인 경우가 55예였다(Table 3). 추적기간 중 35예가 사망하였고 평균 추적기간은 58.9 (13.3)개월이었으며, 사망한 이들의 평균(SD) 생존기간은 약 64.4 (13.1)개월이었고, 5년 생존율은 77%였다(Table 4). 생존율과 유의한 관련성을 보인 변수는 암 병기(P 0.01) 와 림프절 전이여부였으며(P 0.01), 특히 암 병기 3기가 유의하게 낮은 생존율을 보였고 림프절 전이가 많을수록, 핵 등급이 나쁠수록(P 0.01), 호르몬 수용체가 없는 경우 역시 생존율이 유의하게 낮았다(P 0.01)(Table 2). 2) HER-2/neu의 발현 유방암에서 HER-2/neu 종양유전자의 발현율은 47%였 고, 조직학적 유형에 따른 발현율은 통계학적 의미는 없
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Estimate probability 1.0.8.6 HER-2/neu.4 Positive.2 Nevative 0.0 30 40 50 60 70 80 90 Month
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