0049 αb crystallin as a novel marker of lymph node metastasis in breast cancer

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S30 Poster Session I. Predictive and prognostic factors Thursday, 12 March 2009 0049 aB crystallin as a novel marker of lymph node metastasis in breast cancer L. Kim 1 , T. Eom 1 , H. Kang 2 , C. Jeon 3 . 1 Division of breast and endocrine surgery, Hallym University Sacred Heart Hospital, Anyang, 2 Division of breast and endocrine surgery, Hangang Sacred Heart Hospital, Seoul, 3 Division of breast surgery, Kosin University Gospel Hospital, Busan, South Korea Goals: aB-crystallin, the member of small heat shock protein, is known as an anti-apoptotic protein and is associated with aggressive tumor behaviour. In addition, recent study revealed that aB-crystallin was over- expressed in a metastatic variant of the GI101A human breast carcinoma cell line. The purpose of this study was to investigate whether expression of aB-crystallin was associated with lymph node metastasis. And also we evaluated the relationship of expression of aB-crystallin and other established prognostic factors. Methods: Eighty two patients who underwent breast cancer surgery and chemotherapy at Hallym Sacred Heart hospital were enrolled. Ex- pression of aB-crystallin was determined by immunohistochemical staining using monoclonal antibody (SPA-222, Stressgen Biotech, Victoria, British Columbia, Canada) and graded as negative = 0, weakly positive = 1, moderately positive = 2 and highly positive = 3. Estrogen receptor, pro- gesterone receptor, HER-2, lymphatic tumor emboli, histologic grades and other tumor markers were compared with aB-crystallin expression. Results: Expression of aB-crystallin in breast cancer tissues was as- sociated with lymph node metastasis (p = 0.01), lymphatic tumor em- boli (p < 0.01), high nuclear grade (p = 0.02) and triple negative status (p = 0.02). Five of 6 visceral metastasis cases showed highly expression of aB-crystallin. Conclusion: A strong relationship between aB-crystallin expression and lymph node metastasis and visceral metastasis in breast cancer. And also the expression of aB-crystallin significantly correlated with Triple Negative Breast Cancer. We suggest that aB-crystallin could be a novel marker of lymph node metastasis and a good prognostic factor of breast cancer. 0050 Expression of ER, p53 and HER-2/neu in medullary carcinoma and infiltrating ductal carcinoma with medullary feature S. Kim 1 , M. Lee 2 , H. Woo 2 , S. Han 1 , C. Lim 3 , D. Sohn 4 , E. Kim 5 . 1 General Surgery, Soonchunhyang University Hospital, Cheonan, 2 General Surgery, Soonchunhyang University Hospital, Seoul, 3 General Surgery, Soonchunhyang University Hospital, Buchen, 4 General Surgery, Soonchunhyang University Hospital, Gumi, 5 Pathology, Soonchunhyang University Hospital, Cheonan, South Korea Goals: Breast cancer with BRCA1 variation has similar microscopic appearance with medullary cancer, and has pushing margins. These cases are classified as infiltrating ductal carcinoma with medullary fea- ture nowadays. In general, medullary cancer expresses positive p53 and negative HER-2/neu. Positive ER is related to good prognosis, and well differentiated cancer is related to positive predictive value. Based on these correlations, the study was designed to make differentiation between medullary cancer and infiltrating ductal carcinoma with medullary feature with expression of ER, p53, and HER-2/neu. Methods: Specimen of 12 medullary cancer and 19 infiltrating ductal carcinoma with medullary feature, which were obtained from biopsy or operation at breast clinic in Soonchunhyang university Cheonan hospital underwent immunohistochemistry stain. Results: ER expression in medullary cancer was negative in 9 out of 10 cases. In infiltrating ductal carcinoma with medullary feature, it was negative in 14 out of 20 cases, and there was expression of grade 3 in 5 cases. Expression of p53 in medullary cancer was 1+ in 5, and 3+ in 5 among 10 cases. In infiltrating ductal carcinoma with medullary feature, it was 1+ in 7, and 3+ in 11 among 20 cases. The expression of HER-2/neu in medullary cancer was score 0 in 2, and score 3 in 4 among 10 cases. It was expressed as score 0 in 8, and score 3 in 10 among 20 cases with infiltrating ductal carcinoma with medullary feature. Conclusion: Expression of p53 and HER-2/neu was not useful in differ- entiating medullary cancer and infiltrating ductal carcinoma with medullary feature. ER was useful only in cases with positive ER expression. Micro- scopic findings of necrosis and stromal feature, or ultrasonographic find- ings of tumor margin were considered to be more valuable in discriminating the 2 diseases. 0051 Serum VEGF-C and serum VEGF-R2 in patients with triple negative breast cancer R. Iosifidou 1 , G. Galaktidou 2 , D. Lola 1 , A. Papanikolaou 1 , N. Vladika 3 , F. Patakiouta 3 , A. Bousoulegas 1 . 1 3rd Surgical Clinic, 2 Clinical Research, 3 Pathology Department, Anticancer Hospital Theageneio, Thessaloniki, Greece Goals: Triple negative breast cancer (ER-PR-HER2 negative) is not very common, has very poor prognosis and his therapeutic approach has become a major problem. Elevated VEGF-C levels have been correlated with many cancers and expression may be a predictor of lymph node metastases. VEGF- R2 plays an important role in tumor angiogenesis. In our study we measured VEGF-C and VEGF- R2 in serum as an effort to find prognostic factors for this special subgroup. Methods: During the last five years we have operated 76 patients with triple negative breast cancer and two patients had core biopsy and preoperative chemotherapy. The mean age of them was 59.41±10.5 y. Tumor size was <2 cm in 30 patients, >2 cm and <5 cm in 19, >5 cm in 27. 17 patients had multifocal breast cancer. 29 patients were node negative, 14 had <3 positive lymph node and 33 had >3 positive lymph node. Histological type was invasive ductal carcinoma in 67 patients, 5 medullary carcinoma, 3 mucinous, 2 invasive lobular and 1 had DCIS. All the patients had chemotherapy and radiotherapy after the surgical treatment. 14 patients had distant metastases, 6 during the first year of their follow-up and 8 during the second year and 5 patients died during the first two years of their follow-up. From the 73 patients who they are alive 29 are in follow-up for less than one year, 10 for >2, 12 for >3 and 22 for >4 years. The percentage of early distant metastases and death in our study is 17.5% and 6.4%. Serum VEGF-C and serum VEGF- R2 were measured in 73 patients who were alive with the method of ELISA. Results: Serum VEGF-C was overexpressed in 77% of patients with triple negative breast cancer. (11393±2160 pg/ml, normal values: 2459– 6651 pg/ml). Serum VEGF- R2 was overexpressed in the same patients with triple negative breast cancer (8948±1234pg/ml, normal values: 2000– 6000 pg/ml). Conclusion: Patients with triple negative breast cancer have poor prognosis as they have high percentage of early distant metastases and death. Overexpression of VEGF-C and VEGF- R2 in our study confirms this fact as VEGF-C is a predictor of lymph node metastases and VEGF- R2 plays an important role in tumor angiogenesis. May be treatments who can block both of them will reduce the percentage of early distant metastases in patients with triple negative breast cancer. 0052 Site-specific relapse pattern of the triple negative tumors in Chinese breast cancer patients Y. Lin 1 , W. Yin 1 , L. Zhou 1 , J. Lu 1 , G. Di 1 , J. Wu 1 , K. Shen 1 , Q. Han 1 , Z. Shen 1 , Z. Shao 1 . 1 Department of Breast Surgery, Cancer Hospital, Fudan University, Shanghai, China Goals: It has been reported that triple negative phenotype is characterized by aggressive clinical history in Western breast cancer patients. Consider- ing racial disparities, however, we sought to analyze the spread pattern for different sites of first recurrence in Chinese triple negative breast cancers. Methods: A retrospective study of 1662 patients was carried out from a large database of breast cancer patients undergoing surgery between January 1, 2000 and March 31, 2004 in Cancer Hospital, Fudan University, Shanghai, China. Survival curves were performed with Kaplan–Meier method and annual recurrence hazard were estimated by hazard function. Results: We found a statistically significant difference in relapse-free survival (RFS) for locoregional and visceral failure (log-rank P = 0.007 and P = 0.025, respectively) among the triple negative, ERBB2+ and HR+/ERBB2− subgroups. In the multivariate Cox proportional hazards regression analysis, RFS for either locoregional or visceral relapse in triple negative category was inferior to that in HR+/ERBB2− patients (P = 0.027 and P = 0.005, respectively), but comparable to that in ERBB2+ women (P = 0.221 and P = 0.889, respectively). Furthermore, the early recurrence peak appeared later in triple negative group than that in ERBB2+ coun- terpart for both locoregional and visceral relapse. On the other hand, it

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Page 1: 0049 αB crystallin as a novel marker of lymph node metastasis in breast cancer

S30 Poster Session I. Predictive and prognostic factors Thursday, 12 March 2009

0049 aB crystallin as a novel marker of lymph node metastasis in

breast cancer

L. Kim1, T. Eom1, H. Kang2, C. Jeon3. 1Division of breast and endocrinesurgery, Hallym University Sacred Heart Hospital, Anyang, 2Division ofbreast and endocrine surgery, Hangang Sacred Heart Hospital, Seoul,3Division of breast surgery, Kosin University Gospel Hospital, Busan,South Korea

Goals: aB-crystallin, the member of small heat shock protein, is knownas an anti-apoptotic protein and is associated with aggressive tumorbehaviour. In addition, recent study revealed that aB-crystallin was over-expressed in a metastatic variant of the GI101A human breast carcinomacell line. The purpose of this study was to investigate whether expressionof aB-crystallin was associated with lymph node metastasis. And alsowe evaluated the relationship of expression of aB-crystallin and otherestablished prognostic factors.

Methods: Eighty two patients who underwent breast cancer surgeryand chemotherapy at Hallym Sacred Heart hospital were enrolled. Ex-pression of aB-crystallin was determined by immunohistochemical stainingusing monoclonal antibody (SPA-222, Stressgen Biotech, Victoria, BritishColumbia, Canada) and graded as negative = 0, weakly positive = 1,moderately positive = 2 and highly positive = 3. Estrogen receptor, pro-gesterone receptor, HER-2, lymphatic tumor emboli, histologic grades andother tumor markers were compared with aB-crystallin expression.

Results: Expression of aB-crystallin in breast cancer tissues was as-sociated with lymph node metastasis (p = 0.01), lymphatic tumor em-boli (p< 0.01), high nuclear grade (p = 0.02) and triple negative status(p = 0.02). Five of 6 visceral metastasis cases showed highly expressionof aB-crystallin.

Conclusion: A strong relationship between aB-crystallin expression andlymph node metastasis and visceral metastasis in breast cancer. And alsothe expression of aB-crystallin significantly correlated with Triple NegativeBreast Cancer. We suggest that aB-crystallin could be a novel marker oflymph node metastasis and a good prognostic factor of breast cancer.

0050 Expression of ER, p53 and HER-2/neu in medullary

carcinoma and infiltrating ductal carcinoma with medullary

feature

S. Kim1, M. Lee2, H. Woo2, S. Han1, C. Lim3, D. Sohn4, E. Kim5.1General Surgery, Soonchunhyang University Hospital, Cheonan,2General Surgery, Soonchunhyang University Hospital, Seoul, 3GeneralSurgery, Soonchunhyang University Hospital, Buchen, 4General Surgery,Soonchunhyang University Hospital, Gumi, 5Pathology, SoonchunhyangUniversity Hospital, Cheonan, South Korea

Goals: Breast cancer with BRCA1 variation has similar microscopicappearance with medullary cancer, and has pushing margins. Thesecases are classified as infiltrating ductal carcinoma with medullary fea-ture nowadays. In general, medullary cancer expresses positive p53 andnegative HER-2/neu. Positive ER is related to good prognosis, and welldifferentiated cancer is related to positive predictive value. Based onthese correlations, the study was designed to make differentiation betweenmedullary cancer and infiltrating ductal carcinoma with medullary featurewith expression of ER, p53, and HER-2/neu.

Methods: Specimen of 12 medullary cancer and 19 infiltrating ductalcarcinoma with medullary feature, which were obtained from biopsy oroperation at breast clinic in Soonchunhyang university Cheonan hospitalunderwent immunohistochemistry stain.

Results: ER expression in medullary cancer was negative in 9 out of10 cases. In infiltrating ductal carcinoma with medullary feature, it wasnegative in 14 out of 20 cases, and there was expression of grade 3 in 5cases. Expression of p53 in medullary cancer was 1+ in 5, and 3+ in 5among 10 cases. In infiltrating ductal carcinoma with medullary feature, itwas 1+ in 7, and 3+ in 11 among 20 cases. The expression of HER-2/neuin medullary cancer was score 0 in 2, and score 3 in 4 among 10 cases.It was expressed as score 0 in 8, and score 3 in 10 among 20 cases withinfiltrating ductal carcinoma with medullary feature.

Conclusion: Expression of p53 and HER-2/neu was not useful in differ-entiating medullary cancer and infiltrating ductal carcinoma with medullaryfeature. ER was useful only in cases with positive ER expression. Micro-scopic findings of necrosis and stromal feature, or ultrasonographic find-

ings of tumor margin were considered to be more valuable in discriminatingthe 2 diseases.

0051 Serum VEGF-C and serum VEGF-R2 in patients with

triple negative breast cancer

R. Iosifidou1, G. Galaktidou2, D. Lola1, A. Papanikolaou1, N. Vladika3,F. Patakiouta3, A. Bousoulegas1. 13rd Surgical Clinic, 2Clinical Research,3Pathology Department, Anticancer Hospital Theageneio, Thessaloniki,Greece

Goals: Triple negative breast cancer (ER-PR-HER2 negative) is not verycommon, has very poor prognosis and his therapeutic approach hasbecome a major problem. Elevated VEGF-C levels have been correlatedwith many cancers and expression may be a predictor of lymph nodemetastases. VEGF- R2 plays an important role in tumor angiogenesis. Inour study we measured VEGF-C and VEGF- R2 in serum as an effort tofind prognostic factors for this special subgroup.

Methods: During the last five years we have operated 76 patientswith triple negative breast cancer and two patients had core biopsy andpreoperative chemotherapy. The mean age of them was 59.41±10.5 y.Tumor size was <2 cm in 30 patients, >2 cm and <5 cm in 19, >5 cmin 27. 17 patients had multifocal breast cancer. 29 patients were nodenegative, 14 had <3 positive lymph node and 33 had >3 positive lymphnode. Histological type was invasive ductal carcinoma in 67 patients, 5medullary carcinoma, 3 mucinous, 2 invasive lobular and 1 had DCIS.All the patients had chemotherapy and radiotherapy after the surgicaltreatment. 14 patients had distant metastases, 6 during the first year oftheir follow-up and 8 during the second year and 5 patients died duringthe first two years of their follow-up. From the 73 patients who they arealive 29 are in follow-up for less than one year, 10 for >2, 12 for >3 and22 for >4 years. The percentage of early distant metastases and death inour study is 17.5% and 6.4%. Serum VEGF-C and serum VEGF- R2 weremeasured in 73 patients who were alive with the method of ELISA.

Results: Serum VEGF-C was overexpressed in 77% of patients withtriple negative breast cancer. (11393±2160 pg/ml, normal values: 2459–6651 pg/ml). Serum VEGF- R2 was overexpressed in the same patientswith triple negative breast cancer (8948±1234pg/ml, normal values: 2000–6000 pg/ml).

Conclusion: Patients with triple negative breast cancer have poorprognosis as they have high percentage of early distant metastases anddeath. Overexpression of VEGF-C and VEGF- R2 in our study confirms thisfact as VEGF-C is a predictor of lymph node metastases and VEGF- R2plays an important role in tumor angiogenesis. May be treatments who canblock both of them will reduce the percentage of early distant metastasesin patients with triple negative breast cancer.

0052 Site-specific relapse pattern of the triple negative tumors in

Chinese breast cancer patients

Y. Lin1, W. Yin1, L. Zhou1, J. Lu1, G. Di1, J. Wu1, K. Shen1, Q. Han1,Z. Shen1, Z. Shao1. 1Department of Breast Surgery, Cancer Hospital,Fudan University, Shanghai, China

Goals: It has been reported that triple negative phenotype is characterizedby aggressive clinical history in Western breast cancer patients. Consider-ing racial disparities, however, we sought to analyze the spread pattern fordifferent sites of first recurrence in Chinese triple negative breast cancers.

Methods: A retrospective study of 1662 patients was carried out froma large database of breast cancer patients undergoing surgery betweenJanuary 1, 2000 and March 31, 2004 in Cancer Hospital, Fudan University,Shanghai, China. Survival curves were performed with Kaplan–Meiermethod and annual recurrence hazard were estimated by hazard function.

Results: We found a statistically significant difference in relapse-freesurvival (RFS) for locoregional and visceral failure (log-rank P=0.007and P=0.025, respectively) among the triple negative, ERBB2+ andHR+/ERBB2− subgroups. In the multivariate Cox proportional hazardsregression analysis, RFS for either locoregional or visceral relapse in triplenegative category was inferior to that in HR+/ERBB2− patients (P = 0.027and P=0.005, respectively), but comparable to that in ERBB2+ women(P=0.221 and P=0.889, respectively). Furthermore, the early recurrencepeak appeared later in triple negative group than that in ERBB2+ coun-terpart for both locoregional and visceral relapse. On the other hand, it