Evaluation of Connexin 43 and 26 in Intraductal Carcinoma and Their Potential Role in Early Mammary Oncogenesis
PJ Zhang, TL Pasha, SW Yum, A Geza. Hospital of the University of Pennsylvania, Philadelphia; Drexel University College of Medicine, Philadelphia; Moffitt Cancer Center, Tampa
Background: Gap junctions (GJ) are tightly packed intercellular channels which allow direct exchange of small molecules between cells. The channels are assembled selectively from a family of >20 proteins called connexin (Cx) which have diverse functions in cell differentiation, proliferation and death via a GJ dependent or independent mechanism. Cx are also known to have diverse effects in tumor biology. However, its role in early mammary oncogensis has not been well studied.
Design: Paraffin sections of 39 DCIS were immunostained with antibodies to Cx43 (CXN-6, 1:250, Santa Cruz, CA) and Cx26 (rabbit polyclonal, 1:100, Zymed, CA). Immunoreactivity was semiquantified based on the labeling intensity (0-3) and %. A score of 0-300 was generated as the product of the intensity score and the % on each case. Cx immunoreactivity was also categorized as high or low by the median in each case and analyzed among normal, fibrocystic and neoplastic epithelia and correlated with nuclear grade, ER/PR/ Her2 status of DCIS.
Results: Normal mammary epithelium showed frequent membranous Cx26 reactivity but little Cx43. In contrast to normal epithelium, Cx43 and Cx26 reactivity tended to be cytoplasmic and was detected in 32 (86%) and 19 of 39 (49%) DCIS, respectively. Cx43 and Cx26 immunoreactivity was significantly different between DCIS and normal epithelium (Table 1).
Cx26 level was marginally correlated to high nuclear grade (P=0.0509). Cx43 or Cx26 reactivity did not correlate with ER, PR or Her2 status in DCIS.
Conclusions: Cx43 is frequently over-expressed in the cytoplasm of DCIS cells. In contrast to the membrane Cx26 reactivity in normal epithelium, a smaller number of DCIS express lower level of cytoplasmic Cx26. The cytoplasmic expression of Cx43 and Cx26 is significant different between DCIS and benign epithelium. It is unclear what is the biologic mechanism for the cytoplasmic accumulation of Cx43 and Cx26 which, nevertheless, may play a role in early mammary oncogenesis. The lack of membrane localization of both Cx43 and Cx26, and the lack of correlation with ER/PR/Her2 status suggest that the functions of these two Cx in DCIS are likely GJ and ER/HER2 independent.
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 30, Tuesday Morning