HIF-1α在乳腺癌及癌前病变中的表达及其与临床病理因素的关系(英文)

Expression of HIF-1α in breast cancer and precancerous lesions and the relationship to clinicopathological features

Objective: The aim of this study was to observe the expressions and clinical significance of HIF-1α in breast cancer and precancerous lesions, and analyze the relationship between the expressions and clinicopathological features in breast cancer. Methods: We analyzed the HIF-1α expression in 128 cases of invasive ductal carcinomas, 146 precancerous lesions patients including 89 cases of ductal carcinoma in situ and 57 cases of atypical ductal hyperplasia. 53 cases of usual ductal hyperplasia breast tissues were selected as a control group. The specimens were evaluated for HIF-1α, estrogen receptor(ER) & progesterone receptor(PR), epidermal growth factor receptor type 2(HER2/neu) and Ki-67. Immunoreactivity was semi-quantitatively evaluated in at least 1000 cells examined under the microscope at 40 × magnification and recorded as the percentage of positive tumor cells over the total number of cells examined in the same area. The percentage scores were subsequently categorized. The express of HIF-1α and their relationship with multiple biological parameters including ER & PR, HER2/neu and Ki-67, the biomarkers levels of CA153, CA125 TSGF, and CEA in blood serum and nipple discharge, histological grade, region lymph node metastasis, distant metastasis and recurrence on files were also assessed. Results: Compared with usual ductal hyperplasia, the positive expression rate of HIF-1α in atypical ductal hyperplasia, ductal carcinoma in situ and invasive ductal carcinomas group was significantly increased(P < 0.01). The positive rates of HIF-1α in invasive ductal carcinomas were 68.75%, which were significantly higher than that in ductal carcinoma in situ(43.8%), atypical ductal hyperplasia(31.6%), usual ductal hyperplasia(9.4%; χ2 = 13.44, 22.27, 52.79, respectively, P < 0.01). Statistical analysis showed that difference of abnormal expression rate of HIF-1α between ductal carcinoma in situ and usual ductal hyperplasia(χ2 = 18.37, P = 0. 00), atypical ductal hyperplasia and usual ductal hyperplasia(χ2 = 8.14, P = 0.00) was significant(P = 0.00). However, no significant difference in the positive expression rate of HIF-1α was found between atypical ductal hyperplasia and ductal carcinoma in situ tissue(χ2 = 2.19, P = 0.14). There was a significantly difference in the mean HIF-1α frequency between ER & PR positive invasive ductal carcinomas group and negative group, epidermal growth factor receptor type 2(HER2/neu) positive and negative groups, Ki-67 proliferation index ≤ 14% and > 14% groups, histological grade(I + II) and grade III invasive ductal carcinomas groups, with lymph node metastasis, distant metastasis and recurrence groups(P < 0.05) and without groups(P < 0.05). However, there was not difference in the mean HIF-1α between age(≤ 50 years vs > 50 years), tumor diameter(≤ 2 cm vs > 2 cm; P > 0.05). The nipple discharge and serum levels of CA153, TSGF, CA125 and CEA in invasive ductal carcinomas HIF-1α positive patients were significantly higher than those in the negative patients(P < 0.05). Conclusion: In breast cancer, HIF-1α expression was abnormally increased. The aberration of HIF-1α may play a key role during oncogenesis(atypical ductal hyperplasia or ductal carcinoma in situ) and promote breast cellular transformation into malignancy, a finding useful for further understanding of tumorigenesis. The abnormal expression of HIF-1α may be as an early event in the development of breast tumor. The over-expression of HIF-1α might be important biological markers for invasion, metastasis and recurrence of breast cancer.

Objective： The aim of this study was to observe the expressions and clinical significance of HIF-1a in breast cancer and precancerous lesions, and analyze the relationship between the expressions and clinicopathological features in breast cancer. Methods： We analyzed the HIF-1a expression in 128 cases of invasive ductal carcinomas, 146 precancerous lesions patients including 89 cases of ductal carcinoma in situ and 57 cases of atypical ductal hyperplasia. 53 cases of usual ductal hyperplasia breast tissues were selected as a control group. The specimens were evaluated for HIF-1a, estrogen receptor （ER） ＆ progesterone receptor （PR）, epidermal growth factor receptor type 2 （HER2/neu） and Ki-67. Immunoreactivity was semi-quantitatively evaluated in at least 1000 cells examined under the microscope at 40 x magnification and recorded as the percentage of positive tumor cells over the total number of cells examined in the same area. The percentage scores were subsequently categorized. The express of HIF-1a and their relationship with multiple biological parameters including ER ＆ PR, HER2/neu and Ki-67, the biomarkers levels of CA153, CA125 TSGF, and CEA in blood serum and nipple discharge, histological grade, region lymph node metastasis, distant metastasis and recurrence on files were also assessed. Results： Compared with usual ductal hyperplasia, the positive expression rate of HIF-1a in atypical ductal hyperplasia, ductal carcinoma in situ and invasive ductal carcinomas group was significantly increased （P 〈 0.01）. The positive rates of HIF-1a in invasive ductal carcinomas were 68.75%, which were significantly higher than that in ductal carcinoma in situ （43.8%）, atypical ductal hyperplasia （31.6%）, usual ductal hyperplasia （9.4%; X2 = 13.44, 22.27, 52.79, respectively, P 〈 0.01）. Statistical analysis showed that difference of abnormal expression rate of HIF-1a between ductal carcinoma in situ and usual ductal hyperplasia （X2 = 18.37, P = 0.00）, atypical ductal hyperplasia and usual ductal hyperplasia （x2 = 8.14, P = 0.00） was significant （P = 0.00）. However, no significant difference in the positive expression rate of HIF-1a was found between atypical ductal hyperplasia and ductal carcinoma in situ tissue （X2 = 2.19, P = 0.14）. There was a significantly difference in the mean HIF-1a frequency between ER ＆ PR positive invasive ductal carcinomas group and negative group, epidermal growth factor receptor type 2 （HER2/neu） positive and negative groups, Ki-67 proliferation index 〈 14% and 〉 14% groups, histological grade （I ＋ II） and grade III invasive ductal carcinomas groups, with lymph node metastasis, distant metastasis and recurrence groups （P 〈 0.05） and without groups （P 〈 0.05）. However, there was not difference in the mean HIF-1a between age （〈 50 years vs 〉 50 years）, tumor diameter （〈 2 cm vs 〉 2 cm; P 〉 0.05）. The nipple discharge and serum levels of CA153, TSGF, CA125 and CEA in invasive ductal carcinomas HIF-1a positive patients were significantly higher than those in the negative patients （P 〈 0.05）. Conclusion： In breast cancer, HIF-1a expressibn was abnormally increased. The aberration of HIF-1a may play a key role during oncogenesis （atypical ductal hyperplasia or ductal carcinoma in situ） and promote breast cellular transformation into malignancy, a finding useful for further understanding of tumorigenesis. The abnormal expression of HIF-1a may be as an early event in the development of breast tumor. The over-expression of HIF-1a might be important biological markers for invasion, metastasis and recurrence of breast cancer.