학술논문
High expression of integrin β6 in association with the Rho-Rac pathway identifies a poor prognostic subgroup within HER2 amplified breast cancers.
Document Type
Article
Author
Desai, Krisha; Nair, Madhumathy G.; Prabhu, Jyothi S.; Vinod, Anupama; Korlimarla, Aruna; Rajarajan, Savitha; Aiyappa, Radhika; Kaluve, Rohini S.; Alexander, Annie; Hari, P. S.; Mukherjee, Geetashree; Kumar, Rekha V.; Manjunath, Suraj; Correa, Marjorrie; Srinath, B. S.; Patil, Shekhar; Prasad, M. S. N.; Gopinath, K. S.; Rao, Raman N.; Violette, Shelia M.
Source
Subject
*INTEGRIN-binding proteins
*DUCTAL carcinoma
*DIAGNOSTIC immunohistochemistry
*HER2 protein
*RHO factor
*PROGNOSIS
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Language
ISSN
2045-7634
Abstract
Integrin αv β6 is involved in the transition from ductal carcinoma in situ ( DCIS) to invasive ductal carcinoma ( IDC) of the breast. In addition, integrin β6 ( ITGB6) is of prognostic value in invasive breast cancers, particularly in HER2+ subtype. However, pathways mediating the activity of integrin αv β6 in clinical progression of invasive breast cancers need further elucidation. We have examined human breast cancer specimens ( N = 460) for the expression of integrin β6 ( ITGB6) mRNA by qPCR. In addition, we have examined a subset ( N = 147) for the expression of αv β6 integrin by immunohistochemistry ( IHC). The expression levels of members of Rho-Rac pathway including downstream genes ( ACTR2, ACTR3) and effector proteinases ( MMP9, MMP15) were estimated by qPCR in the HER2+ subset ( N = 59). There is a significant increase in the mean expression of ITGB6 in HER2+ tumors compared to HR+ HER2- and triple negative ( TNBC) subtypes ( P = 0.00). HER2+ tumors with the highest levels (top quartile) of ITGB6 have significantly elevated levels of all the genes of the Rho-Rac pathway ( P-values from 0.01 to 0.0001). Patients in this group have a significantly shorter disease-free survival compared to the group with lower ITGB6 levels ( HR = 2.9 (0.9-8.9), P = 0.05). The mean level of ITGB6 expression is increased further in lymph node-positive tumors. The increased regional and distant metastasis observed in HER2+ tumors with high levels of ITGB6 might be mediated by the canonical Rho-Rac pathway through increased expression of MMP9 and MMP15. [ABSTRACT FROM AUTHOR]