Neurotensin Receptor 1 (NTSR1) Expression in Breast Carcinomas Is Universal and Independent of ER/PR/Her2
Xianyong Gui, Shuhong Liu, Zu-hua Gao. University of Calgary and Calgary Laboratory Services, Calgary, AB, Canada
Background: Neurotensin (NT) is a 13-AA biopeptide with diverse functions including trophic effects on some normal and neoplastic cells. Most of NT's effects are mediated via high-affinity neurotensin receptor 1 (NTSR1), a member of G-protein-coupled receptor family. NTSR1 activates PKC/RAF/MEK/ERK signaling pathways as well as transactivates EGFR, leading to cell proliferation. It has been found in breast carcinomas that both NT and NTSR1 are overexpressed and are involved in tumor progression. NT/NTSR1 thus becomes a potential therapeutic target. Here we further studied whether the expression of NTSR1 is correlated with that of ER, PR, and Her2.
Design: 52 cases of resected invasive breast carcinomas (age 24-81), including both ductal (44) and lobular (8) types, were retrieved from our 2010 surgical pathology file. ER and PR were routinely assessed by immunohistochemistry, and Her2 was routinely detected by silver in-situ hybridization (SISH). All tumors were graded histologically. Based on their ER/PR profiles, the ductal carcinomas (DCs) were subgrouped into ER+/PR+ (21), ER+/PR- (11), and ER-/PR- (12). The 8 lobular carcinomas (LCs) were all ER+/PR+. The data of Her2 was available in 45 cases. 8 of 38 (21.05%) DCs but none of 7 LCs were Her2 positive. 8 of 11 ER-/PR- DCs were also Her2 negative (triple negative). The expression of NTSR1 was detected by immunohistochemistry, and it was semiquantitated (as negative, 1+, 2+, 3+). A comparison of NTSR1 expressions between these groups was analyzed.
Results: Immunoreactivity of NTSR1 appeared in a cytoplasmic pattern. Non-neoplastic mammary epithelial cells showed a partial and weak positivity. Increased NTSR1 expression was detected in 43/44 (97.73%) DCs (100% in ER+/PR+, 100% in ER+/PR-, and 91.67% in ER-/PR- group), and 8/8 (100%) LCs. And it was seen in 7/8 (87.5%) Her2+ DCs, 30/30 (100%) Her2- DCs, 7/7 (100%) Her2- LCs, and 8/8 (100%) triple negative DCs. No significant difference existed either between tumors with low and high grades, or between ER+ and ER-, PR+ and PR-, or Her2+ and Her2- tumors. However, PR+ DCs showed a slightly stronger expression with more cases showing a 2+ expression as compared with PR- DCs (66.67% in ER+/PR+ DCs vs 36.36% in ER+PR- DCs, p > 0.05).
Conclusions: NTSR1 is universally expressed in both ductal and lobular breast carcinomas and it is independent of ER/PR/Her2 profiles of the tumors. Our data further support the potential benefits of developing NTSR1 blockers in adjuvant therapy of breast carcinomas, particularly for those 'triple negative' tumors.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 281, Wednesday Morning