Lack of Association of Cadherin Expression and Histopathologic Type, Metastasis, or Patient Outcome in Oropharyngeal Squamous Cell Carcinoma: A Tissue Microarray Study

Abstract

Altered cadherin expression is important for metastasis in many carcinomas including head and neck squamous cell carcinoma (SCC). We evaluated E- and N-cadherin expression specifically in oropharyngeal SCC and correlated this with clinical and pathologic features. Oropharyngeal SCC patients with clinical follow up information were identified from clinician databases from 1996 through 2007 and tissue microarrays created. Tumors had been previously typed histopathologically as keratinizing, non-keratinizing, or non-keratinizing with maturation, and had known p16 and human papillomavirus status, respectively. Immunohistochemistry was performed on the microarrays, and staining was evaluated for presence and intensity (0 = negative, 1 = weak, 2 = moderate, 3 = strong) both visually and also with digital image analysis software. Of 154 cases, E-cadherin was expressed in 152 (98.7%) and N-cadherin in 17 (11.5%). Neither E- nor N-cadherin expression was statistically significantly associated with histopathologic type (P = 0.082 and P = 0.228, respectively). E-cadherin staining intensity was not statistically significantly associated with nodal or distant metastasis, either visually or by image analysis, (P = 0.098 and P = 0.963 respectively) nor was N-cadherin (P = 0.228 and P = 0.935 respectively). Neither E- nor N-cadherin expression was associated with death from disease (P = 0.995; P = 0.964, respectively). E-cadherin is extensively expressed by oropharyngeal SCC, even the non-keratinizing type. Our results suggest that cadherin expression may not be a predictor for nodal or distant metastasis in these tumors. Mechanisms independent of cadherin expression may be important for metastases in oropharyngeal SCC.

Changed Expression of E-cadherin and Galectin-9 in Oral Squamous Cell Carcinomas but Lack of Potential as Prognostic Markers

“…Several studies show positive correlation between E-cadherin expression and nodal metastasis (Tanaka et al, 2003;Bosch et al, 2005;Foschini et al, 2008;Foschini et al, 2013) but others including our study, dispute this (Mahomed et al, 2007;Lopes et al, 2009;Mostaan et al, 2011;Ukpo et al, 2012;Rosado et al, 2013). An editorial by Cerezo (2011) DOI:http://dx.doi.org/10.7314/APJCP.2014.15.5.2145 Changed Expression of E-cadherin andGalectin-9 …”

The Clinicopathological Significance of Epithelial Mesenchymal Transition Associated Protein Expression in Head and Neck Squamous Cell Carcinoma

“…A recent TMA study of E-cadherin expression in oropharyngeal squamous cell carcinoma20 failed to show a significant correlation between the expression of E-cadherin and histologic type, nodal and distant metastasis, suggesting that E-cadherin expression may not be a predictor of nodal or distant metastasis in these tumors. The inconsistent results in several studies are limit the use of these markers to predict patient outcome.…”

Pattern of invasion in squamous cell carcinomas of the lower lip and oral cavity

“…These investigations suggested that the probability of complete EMT in OSCC is very low. 9,10 In line with these reports, Pod was used alongside E-and N-Cads to evaluate invasive patterns of OSCC and the results indicated the probability of CCI in these cancers. 3,11 A plethora of molecular pathways and markers is involved in the invasion of cancer cells, however the most popular proteins to define EMT and CCI have been the cadherin family, mesenchymal markers like vimentin and the trans-membrane glycoprotein Pod due to its possible role in CCI.…”

“…The latter was classified into 0 where <1% of tumor cells stained positive; 1, if !1-<40% were positive; 2, when !40-<80% showed immunoreactivity and 3 in cases with !80% staining of neoplastic cells. The multiplication of these values was rated as negative (0), weak (1-2), moderate (3-4) and strong (6)(7)(8)(9). Negative and weak tumors were considered E-and N-cadherin negative, while moderate and strong cases were regarded positive for these markers.…”