- Email: [email protected]
P187 Prognostic and predictive significance of multidrug resistance-associated protein 2 (MRP2) expression and its subcellular localization in breast cancer
S40
Poster Session I. Predictive and prognostic factors
viable tumor cells, invasive or noninvasive, in all resected specimens of the breast. Results: Twenty-six (31.3%) patients were classified as luminal A, 12 (14.5%) were luminal B, 15 (18.1%) were luminal-HER2, 9 (10.8%) were HER2, 10 (12.0%) were basal-like, and 11 (13.3%) were NBTN. The overall response rate was 90.4%, including a complete response in 30 patients and a partial response in 45 patients. The overall pCR rate was 15.5% (12/83). The highest pCR rate (40.0%) was observed in patients with basallike tumors. In triple-negative patients, basal-like patients showed significantly higher pCR rate than NBTN patients (40.0% vs. 9.1%, p = 0.01). There were no cases with pCR in a cohort of luminal-HER2 subtype patients. A higher proportion of luminal B patients had pCR than luminal A patients (25.0% vs. 3.8%, p = 0.01). Conclusion: Our data indicate that breast cancer subtypes are useful predictive biomarkers of pCR in breast cancer patients treated with primary systemic chemotherapy. Disclosure of Interest: None Declared
P185
GATA-3 as a new prognostic marker in breast cancer
L.S. Kim1 , Y. Lee1 , Y.-A. Lim1 . 1 Division of Breast and Endocrine Surgery, Hallym University Sacred Heart Hospital, Anyang, Korea, Republic of Goals: GATA-3 is a transcription factor involved in human cell growth and differentiation and closely associated with clinicopathologic features such as ER (estrogen receptor) expression. It has been suggested that loss of GATA-3 may contribute to tumorigenesis and GATA-3 expression can be a prognostic marker in breast cancer. We evaluated GATA-3 expression by immumohistochemical staining and investigated the role of GATA-3 as a prognostic marker in breast cancer. Methods: Seventy four invasive breast cancer tissues were collected from breast cancer patients. Tissues were stained by immunohistochemistry with GATA-3 monoclonal antibody. Evaluation of GATA-3 expression was done by blind method. GATA-3 expression was scored by sum of intensity and percentage staining of nucleus. Patients were followed up and the mean follow up time was 53.1 months. Results: GATA-3 Expression in breast cancer was significantly associated with ER expression (p = 0.005), low histologic grade (p = 0.049), low nuclear grade (p = 0.016), marginally with PR expression (p = 0.099), but not with tumor size (p = 0.466), lymph node involvement (p = 1.000). GATA-3 expression was not significantly associated with recurrence of triple negative (ER/PR/HER-2 negative) breast cancer recurrence (p = 0.518). But GATA3 was significantly associated with low recurrence rate in non-triple negative breast cancer (p = 0.022) and the significance was more powerful than of ER expression. Conclusion: GATA-3 expression is associated with known good prognostic markers and it is likely that GATA-3 will be a good prognostic marker in breast cancer, especially in non-triple negative breast cancer. Disclosure of Interest: None Declared
P186
Prognostic role of VEGFR1−3 immunoreactivity in breast cancer patients
I.J. Gisterek1 , A. Halon2 , U. Staszek-Szewczyk1 , R. Matkowski1 , J. Szelachowska1 , P. Biecek3 , E. Lata1 , K. Szewczyk1 , J. Kornafel1 . 1 Oncology, 2 Pathology, Medical University, Wroclaw, 3 Faculty of Mathematics, University, Warsaw, Poland Goals: The aim of the study was to evaluate whether assessing the immunoreactivity of VEGFRs may have prognostic value in breast cancer patients. Methods: 277 patients with invasive breast carcinomas in early stage of disease were included in our study. According to TNM system in 182 patients T1 was recognized, in 85 − T2 and in 10 cases higher stage of tumour, N0 in 160 patients. Expression of VEGFR1−3 in specimens from patients with invasive breast carcinoma was evaluated using a standard immunoperoxidase technique. Each case was assessed by counting percentage of cells with expression, intensity of reaction and ratio of these two factors called immunoreactivity and then was calculated according to Remmele score. Results: The expression of VEGFR-1 wasn’t found in 139 (50.2%) specimens, in 135 (48.7%) was weak and only in 3 (1.1%) tissues was strong. In most of the tissues – (177 cases, 63.9%) weak expression of
Thursday, 17 March 2011 VEGFR-2 was assessed, in 95 (34.3%) strong and in 5 cases (1.8%) there was no reaction. Only in one (0.4%) specimen VEGFR-3 expression wasn’t detected, it was weak in 92 (33.3%) and strong in 175 (63.3%) cases. We have found strong correlation between reactivity of VEGFR-1 and VEGFR-2 (p = 3.38e−14 ). The relations between VEGFRs and the stage of disease was established. Furthermore there was correlation between immunoreactivity of VEGFR-2 and histological type of cancer. Moreover there was a strong correlation between VEGFR-3 and PgR expression, also VEGFR-2 and Her2/neu reactivity. Univariate survival analysis showed that tumour size, lymph node status, hormonal status, Her2/neu expression and VEGFR-3 immunoreactivity were of significant prognostic value for OS. On the basis of multivariate Cox regression analysis, tumour size, stage of disease, PgR and VEGFR-3 immunoreactivity were identified as independent prognostic factors. Conclusion: In conclusion, overexpression of VEGFRs is associated significantly with recognized prognostic factors and may play an important role for predicting lymph node metastasis in breast cancer. Furthermore, VEGFR-3 may serve as a significant prognostic factor for long-term survival. Disclosure of Interest: None Declared
P187
Prognostic and predictive significance of multidrug resistance-associated protein 2 (MRP2) expression and its subcellular localization in breast cancer
R. Matkowski1,2 , B. Szynglarewicz1 , I. Gisterek2 , J. Kornafel2 , A. Halon3 . 1 2nd Department of Surgical Oncology, Lower Silesian Oncology Centre, 2 Department of Oncology, 3 Department of Pathomorphology, Wroclaw Medical University, Wroclaw, Poland Goals: Multidrug transporter proteins are best known for their contributions to chemoresistance through the efflux of anticancer drugs from cancer cells. The aim of this study was to assess the expression and subcellular localization of MRP2, member of the ABC-transporters family and to analyze its prognostic and predictive value. Methods: A total of 396 patients with breast cancer (BC) were studied. Following primary surgery, 56% of patients were subjected to chemotherapy, 47% to radiotherapy and 62% to hormonotherapy. Immunohistochemical (IHC) examination for detection of MRP2 was done and evaluated using immunoreactive Remmele’s scale (IRS). Results: MRP2 expression was common, with 100% of tumours with nuclear expression (mean IRS = 6.39±3.13; median = 6) but with different pattern of expression within the nucleus: (1) 30% of tumours with homogeneous nuclear expression – HNE, (2) 26% of tumours with expression within the nuclear membrane – ME and (3) 44% of tumours with heterogeneous expression within nucleus and its membrane – NME. In 66% of cases weak and in 8% moderate cytoplasmic expression was noted. Cytoplasmic MRP2 expression had neither prognostic nor predictive significance. High MRP2 (overall nuclear IRS) expression was associated with good prognosis in the whole group of patients, indicated significantly increased survival in patients withoutaxillary lymph nodes metastases (ALNM) and less markedly in patients with luminal A and triple negative breast cancers (TNBC). HNE pattern of MRP2 expression was highly associated with good prognosis in patients without ALNM and less evidently – in cases of TNBC. Lack of HNE pattern of MRP2 expression was typical for medullar histology and multivisceral model of dissemination. The multivariate analysis confirmed the prognostic significance (limited to DFS in patients without ALNM) of both: MRP2 expression and its localization. Conclusion: This study supports the concept of MRP2 as promising marker of prognosis particularly in BC patients without lymph node metastases but does not confirm MRP2 value as marker of response to chemotherapy, hormonotherapy or radiotherapy. Disclosure of Interest: None Declared
P188
Could the lack of expression of steroid receptors and HER2 discriminate a subgroup of triple negative breast cancer patients with poorer prognosis?
M.M. Milovic-Kovacevic1 , S. Susnjar1 , A. Karaferic1 , D. Gavrilovic1 , Lj. Stamatovic1 , Z. Milovanovic1 , A. Jovicevic1 . 1 Medical oncology, Institute For Oncology and Radiology of Serbia, Belgrade, Serbia Goals: We investigate if pts with TNBC that lack the expression of ER, PR and HER2 (ER0/PR0/HER2:0) (TN0 subgroup) had poorer disease
Poster Session I. Predictive and prognostic factors
viable tumor cells, invasive or noninvasive, in all resected specimens of the breast. Results: Twenty-six (31.3%) patients were classified as luminal A, 12 (14.5%) were luminal B, 15 (18.1%) were luminal-HER2, 9 (10.8%) were HER2, 10 (12.0%) were basal-like, and 11 (13.3%) were NBTN. The overall response rate was 90.4%, including a complete response in 30 patients and a partial response in 45 patients. The overall pCR rate was 15.5% (12/83). The highest pCR rate (40.0%) was observed in patients with basallike tumors. In triple-negative patients, basal-like patients showed significantly higher pCR rate than NBTN patients (40.0% vs. 9.1%, p = 0.01). There were no cases with pCR in a cohort of luminal-HER2 subtype patients. A higher proportion of luminal B patients had pCR than luminal A patients (25.0% vs. 3.8%, p = 0.01). Conclusion: Our data indicate that breast cancer subtypes are useful predictive biomarkers of pCR in breast cancer patients treated with primary systemic chemotherapy. Disclosure of Interest: None Declared
P185
GATA-3 as a new prognostic marker in breast cancer
L.S. Kim1 , Y. Lee1 , Y.-A. Lim1 . 1 Division of Breast and Endocrine Surgery, Hallym University Sacred Heart Hospital, Anyang, Korea, Republic of Goals: GATA-3 is a transcription factor involved in human cell growth and differentiation and closely associated with clinicopathologic features such as ER (estrogen receptor) expression. It has been suggested that loss of GATA-3 may contribute to tumorigenesis and GATA-3 expression can be a prognostic marker in breast cancer. We evaluated GATA-3 expression by immumohistochemical staining and investigated the role of GATA-3 as a prognostic marker in breast cancer. Methods: Seventy four invasive breast cancer tissues were collected from breast cancer patients. Tissues were stained by immunohistochemistry with GATA-3 monoclonal antibody. Evaluation of GATA-3 expression was done by blind method. GATA-3 expression was scored by sum of intensity and percentage staining of nucleus. Patients were followed up and the mean follow up time was 53.1 months. Results: GATA-3 Expression in breast cancer was significantly associated with ER expression (p = 0.005), low histologic grade (p = 0.049), low nuclear grade (p = 0.016), marginally with PR expression (p = 0.099), but not with tumor size (p = 0.466), lymph node involvement (p = 1.000). GATA-3 expression was not significantly associated with recurrence of triple negative (ER/PR/HER-2 negative) breast cancer recurrence (p = 0.518). But GATA3 was significantly associated with low recurrence rate in non-triple negative breast cancer (p = 0.022) and the significance was more powerful than of ER expression. Conclusion: GATA-3 expression is associated with known good prognostic markers and it is likely that GATA-3 will be a good prognostic marker in breast cancer, especially in non-triple negative breast cancer. Disclosure of Interest: None Declared
P186
Prognostic role of VEGFR1−3 immunoreactivity in breast cancer patients
I.J. Gisterek1 , A. Halon2 , U. Staszek-Szewczyk1 , R. Matkowski1 , J. Szelachowska1 , P. Biecek3 , E. Lata1 , K. Szewczyk1 , J. Kornafel1 . 1 Oncology, 2 Pathology, Medical University, Wroclaw, 3 Faculty of Mathematics, University, Warsaw, Poland Goals: The aim of the study was to evaluate whether assessing the immunoreactivity of VEGFRs may have prognostic value in breast cancer patients. Methods: 277 patients with invasive breast carcinomas in early stage of disease were included in our study. According to TNM system in 182 patients T1 was recognized, in 85 − T2 and in 10 cases higher stage of tumour, N0 in 160 patients. Expression of VEGFR1−3 in specimens from patients with invasive breast carcinoma was evaluated using a standard immunoperoxidase technique. Each case was assessed by counting percentage of cells with expression, intensity of reaction and ratio of these two factors called immunoreactivity and then was calculated according to Remmele score. Results: The expression of VEGFR-1 wasn’t found in 139 (50.2%) specimens, in 135 (48.7%) was weak and only in 3 (1.1%) tissues was strong. In most of the tissues – (177 cases, 63.9%) weak expression of
Thursday, 17 March 2011 VEGFR-2 was assessed, in 95 (34.3%) strong and in 5 cases (1.8%) there was no reaction. Only in one (0.4%) specimen VEGFR-3 expression wasn’t detected, it was weak in 92 (33.3%) and strong in 175 (63.3%) cases. We have found strong correlation between reactivity of VEGFR-1 and VEGFR-2 (p = 3.38e−14 ). The relations between VEGFRs and the stage of disease was established. Furthermore there was correlation between immunoreactivity of VEGFR-2 and histological type of cancer. Moreover there was a strong correlation between VEGFR-3 and PgR expression, also VEGFR-2 and Her2/neu reactivity. Univariate survival analysis showed that tumour size, lymph node status, hormonal status, Her2/neu expression and VEGFR-3 immunoreactivity were of significant prognostic value for OS. On the basis of multivariate Cox regression analysis, tumour size, stage of disease, PgR and VEGFR-3 immunoreactivity were identified as independent prognostic factors. Conclusion: In conclusion, overexpression of VEGFRs is associated significantly with recognized prognostic factors and may play an important role for predicting lymph node metastasis in breast cancer. Furthermore, VEGFR-3 may serve as a significant prognostic factor for long-term survival. Disclosure of Interest: None Declared
P187
Prognostic and predictive significance of multidrug resistance-associated protein 2 (MRP2) expression and its subcellular localization in breast cancer
R. Matkowski1,2 , B. Szynglarewicz1 , I. Gisterek2 , J. Kornafel2 , A. Halon3 . 1 2nd Department of Surgical Oncology, Lower Silesian Oncology Centre, 2 Department of Oncology, 3 Department of Pathomorphology, Wroclaw Medical University, Wroclaw, Poland Goals: Multidrug transporter proteins are best known for their contributions to chemoresistance through the efflux of anticancer drugs from cancer cells. The aim of this study was to assess the expression and subcellular localization of MRP2, member of the ABC-transporters family and to analyze its prognostic and predictive value. Methods: A total of 396 patients with breast cancer (BC) were studied. Following primary surgery, 56% of patients were subjected to chemotherapy, 47% to radiotherapy and 62% to hormonotherapy. Immunohistochemical (IHC) examination for detection of MRP2 was done and evaluated using immunoreactive Remmele’s scale (IRS). Results: MRP2 expression was common, with 100% of tumours with nuclear expression (mean IRS = 6.39±3.13; median = 6) but with different pattern of expression within the nucleus: (1) 30% of tumours with homogeneous nuclear expression – HNE, (2) 26% of tumours with expression within the nuclear membrane – ME and (3) 44% of tumours with heterogeneous expression within nucleus and its membrane – NME. In 66% of cases weak and in 8% moderate cytoplasmic expression was noted. Cytoplasmic MRP2 expression had neither prognostic nor predictive significance. High MRP2 (overall nuclear IRS) expression was associated with good prognosis in the whole group of patients, indicated significantly increased survival in patients withoutaxillary lymph nodes metastases (ALNM) and less markedly in patients with luminal A and triple negative breast cancers (TNBC). HNE pattern of MRP2 expression was highly associated with good prognosis in patients without ALNM and less evidently – in cases of TNBC. Lack of HNE pattern of MRP2 expression was typical for medullar histology and multivisceral model of dissemination. The multivariate analysis confirmed the prognostic significance (limited to DFS in patients without ALNM) of both: MRP2 expression and its localization. Conclusion: This study supports the concept of MRP2 as promising marker of prognosis particularly in BC patients without lymph node metastases but does not confirm MRP2 value as marker of response to chemotherapy, hormonotherapy or radiotherapy. Disclosure of Interest: None Declared
P188
Could the lack of expression of steroid receptors and HER2 discriminate a subgroup of triple negative breast cancer patients with poorer prognosis?
M.M. Milovic-Kovacevic1 , S. Susnjar1 , A. Karaferic1 , D. Gavrilovic1 , Lj. Stamatovic1 , Z. Milovanovic1 , A. Jovicevic1 . 1 Medical oncology, Institute For Oncology and Radiology of Serbia, Belgrade, Serbia Goals: We investigate if pts with TNBC that lack the expression of ER, PR and HER2 (ER0/PR0/HER2:0) (TN0 subgroup) had poorer disease