Meme kanserinde carbonic anhydrase IX ve Hipoxia inducible factor-1 alpha ekspresyonlarının değerlendirilmesi


Thesis Type: Expertise In Medicine

Institution Of The Thesis: Gazi Üniversitesi, Tıp Fakültesi, Turkey

Approval Date: 2008

Student: ALİ OSMAN KAYA

Supervisor: NAZAN GÜNEL

Abstract:

111 women patients with breast cancer followed up by Medical Oncology Department of Gazi University Medical School in a period between June 1996 and February 2008 are included in the study. Two groups are set with 56 estrogen progesterone receptor positive, Her-2/neu negative patients and 55 estrogen progesterone receptor negative, Her-2/neu positive patients. HIF 1 alpha and CA IX expressions are investigated in both groups and compared with each other. Values of HIF-1 alpha expression above 2% are considered as positive and fewer than 2% (nuclear staining ratio) are considered as negative. For CA IX expression any membranous staining is accepted as positive and if there was no staining the samples were accepted as negative. Additionally, relation of HIF 1 alpha and CA IX expressions with stage, grade, lymph node metastasis, tumor dimensions and menopause is also examined. Median age of patients in group 1 was 52 (range 34-77), and median age of patients in group 2 was 47 (range: 27-83). 23 (41, 1 %) of patients in group 1 were premenopausal and 33 of them (60 %) were postmenopausal. 33 (60%) of patients in group 2 were premenopausal and 22 of them (40 %) were postmenopausal. In 26 (% 46.4) of 56 estrogen and progesterone receptor positive/ Her-2/neu negative (group 1) patients HIF-1alpha expression was detected as nuclear positive and in remaining 30 patients (% 53.6) any HIF-1 alpha expression was not detected. 46 (% 83.6) of 55 estrogen and progesterone receptor negative/ Her-2/neu positive patients (Group 2) HIF-1 alpha expression was nuclear positive and in 9 patients (%16.4) nuclear staining was negative. Group 2 produced more positive results for HIF-1 alpha expression when compared to Group 1. The difference between two groups was statistically significant (p< 0.0001). In 25 (% 46.4) of 56 estrogen and progesterone receptor positive/ Her-2/neu negative (group 1) patients CA IX expression was detected as membranous positive and in remaining 31 patients (% 55,4) any CA IX expression was not detected. 37 (% 67.3) of 55 estrogen and progesterone receptor negative/ Her-2/neu positive patients (Group 2) CA IX expression was membranous positive and in 18 patients (%32.7) membranous staining was negative. Group 2 produced more positive results for CA IX expression when compared to Group 1. The difference between two groups was statistically significant (p< 0.013). In group 1, there were one grade 1 patient (1,8 %), 43 grade 2 patients (76,8 %) and 12 grade 3 patients (21,4 %). In group 2 there were no grade 1 patient, 24 grade 2 patients (43,6 %) and 31 Grade 3 patients (56,4 %). Difference in tumor grades between groups was statistically significant (p=0.001). When two groups were compared for tumor size and lymph node status no statistically significant difference was detected (p=0.383, p=0.703). . Median disease free survival in group 1 was not reached. Mean survival time was 88.35 ±6.73 months. For group 2\ median disease free survival was 46 months (%95 CI: 42.98-49.02). Median disease free survival duration found to be shorter in endocrine insensitive Her-2/neu positive (Group 2) patients. Difference between two groups was significant. (log-rank p= 0.0308). In group 1, median overall survival was 108 months ( 95% CI: 90.65-125.35). In group 2, median overall survival was 75 months (95 % CI: 64.94-85.06). Difference between two groups was statistically significant. (log-rank p= 0.0339) In conclusion, hypoxic tumor indicators HIF-1 alpha and CA IX expressions are observed more in ER and PR negative, Her-2/neu (c-erbB2) positive breast cancer. For the patients with HIF-1 alpha and CA IX over expression, disease free survival and total survival durations are shorter.