Immunoexpression of programmed cell death 4 protein in normal oral mucosa, oral epithelial dysplasia and oral squamous cell carcinoma

Abstract

Background:Oral squamous cell carcinoma (OSCC) is the frequently reported cancer of the head and neck. Recent studies are being conducted to evaluate the role of potential markers for diagnosing the stages of development of OSCC from normal cells.Aim:The aim of this study is to evaluate and compare the immunoexpression of programmed cell death 4 (PDCD4) protein in normal oral mucosa, oral epithelial dysplasia (OED) and OSCC.Materials and Methods:Histologically diagnosed, formalin-fixed paraffin-embedded archived cases (n = 100) of normal mucosa (n = 10), OED (n = 60) and OSCC (n = 30) were analyzed immunohistochemically in the present retrospective study using monoclonal rabbit antihuman PDCD4. OED and squamous cell carcinoma were graded according to the World Health Organization and Broder's histological grading criteria, respectively. Clinical parameters and immunohistochemical results were analyzed by Fisher exact test using SPSS software. P <0.05 was indicative of significant differences.Results:PDCD4 expression was observed in the normal oral mucosa, OED and OSCC. The maximum expression was observed in the normal oral mucosa, which reduced significantly in OED and OSCC (P = 0.017). With the increase in the transformation from normal cells to cancer cells, a shift from nuclear to cytoplasmic staining was observed indicating predominant cytoplasmic localization of stain as a feature of altered cells.Conclusion:The present study delineates the molecular difference between the normal, dysplastic and carcinomatous cells; and points toward the role of PDCD4 localization in the proliferation of cells. This study thus highlights the need for further research with inclusion of long follow-up period and other pathological criteria such as inflammation and microenvironment, immune status of patient and tumor stage, which could aid in the development of prospective diagnostic options.

Potential Immunohistochemical Biomarkers for Grading Oral Dysplasia: A Literature Review

“…PDCD4 expression was observed in normal oral mucosa, OED, and OSCC. Desai and Kale [ 128 ] showed that the maximum expression was observed in normal oral mucosa, which reduced significantly in OED and OSCC.…”

“…Cell division and proliferation p53 [53][54][55]75,76,117], Ki-67 [56,[68][69][70][71][72][73][74][75][76], CD105 [73,74], p63 [39,42,117], CD31 [39], CD34 [43], cycD1 [42], VEGF [43], YAP, Np63 [59], stathmin [80], CDKN1A [53] Epithelial-mesenchymal transition CK5\6 [96], CK19 [98], β-catenin [103,104], N-cadherin [109], E-cadherin [104][105][106][107], TWIST [111], VIM [107,108], PDPN [115,117], MMP-9 [108] Cell death regulation Bcl-2 [123,124], PDCD4 [128], HSP27 [131], cornulin [134] Cellular metabolism HIF-1a [136], iNOS...…”

Low PDCD4 Expression Is Associated With Poor Prognosis of Colorectal Carcinoma

“…On the basis of nuclear-cytoplasmic shuttling of PDCD4, decreased nuclear expression might be indicative of cellular derangement or tumoral transition 12. In previous studies, overall reduction, nuclear loss, and transition from the nucleus to the cytoplasm of PDCD4 were evaluated and all were correlated with poor survival of cancer patients 12,30. However, Mudduluru et al12 reported that cancer cells may not contain PDCD4 in the nucleus because of an overall reduction of total PDCD4 in cancer cells; therefore, decreased nuclear expression may represent the overall reduction in total PDCD4 in cancer cells, which is a readily visible and convenient way to evaluate through IHC.…”

“…12 In previous studies, overall reduction, nuclear loss, and transition from the nucleus to the cytoplasm of PDCD4 were evaluated and all were correlated with poor survival of cancer patients. 12,30 However, Mudduluru et al 12 reported that cancer cells may not contain PDCD4 in the nucleus because of an overall reduction of total PDCD4 in cancer cells; therefore, decreased nuclear expression may represent the overall reduction in total PDCD4 in cancer cells, which is a readily visible and convenient way to evaluate through IHC. Therefore, the nuclear expression has been mainly evaluated in recent studies on PDCD4, 31,32 and the present study exhibited a significant result of nuclear expression of PDCD4.…”

<p>Aberrant Expression Of PDCD4/eIF4A1 Signal Predicts Postoperative Recurrence For Early-Stage Oral Squamous Cell Carcinoma</p>

“…Although one study has investigated the role of PDCD4 in OSCC,12 little is known about the co-expression pattern and prognostic value of PDCD4 and eIF4A1 in the same tumor. Ovarian cancer patients with lower PDCD4 expression were found to have shorter disease-free survival 13.…”