Expression of podoplanin, CD44, and p63 in squamous cell carcinoma of the lung

Abstract

Recent molecular biological studies have identified podoplanin as a candidate cancer stem cell (CSC) marker in squamous cell carcinoma (SqCC). The purpose of this study was to examine the expression pattern of podoplanin, and the other stem cell markers CD44 and p63, and their relationship to clinico-pathological features including survival in pulmonary SqCC. We examined histologically the expression of podoplanin, CD44, and p63 in 162 consecutive SqCC by immunostaining. Podoplanin expression was observed in 107 (66%) tumors, CD44 in 145 (89.5%), and p63 in 151 (93.2%), respectively. In 95.3% of the podoplanin-positive tumors, tumor cells showing strong expression were localized in the periphery of the tumor nests. However, this peripheral localization was observed in only 55.9% of the CD44-positive and 43% of p63-positive tumors. In 88.8% of the podoplanin-positive tumors, positive cells were localized more peripherally in the tumor nests than CD44-or p63-positive cells and when CD44 and p63 expressions were compared in these podoplanin-positive tumors, p63-positive layers in the periphery of the tumor nests were broader compared to CD44-positive layers. These findings suggest tumor cells are aligned in the ''hierarchical distribution pattern'' according to the expression of these three markers. Patients who had podoplanin-positive tumors with the ''hierarchical pattern'' resulted in significantly better overall survival than those who had podoplanin-negative tumors (P = 0.043). These results suggest that podoplanin expression would reflect the most immature status in the differentiation process of SqCC, and SqCC with hierarchical expression would be a well-organized tumor group with lower biological aggressiveness based on the CSC concept.

Podoplanin and SOX2 expression in esophageal squamous cell carcinoma after neoadjuvant chemo-radiotherapy

“…Shimada et al reported that podoplanin expression reflected the immature status in lung squamous cell carcinoma cells. They also found that immunostaining of podoplanin, CD44 and p63 and analysis of the hierarchical distribution patterns of the markers in the tumor nests revealed cells with a capacity for further maturation (24). Long et al demonstrated that SOX2 was implicated in the maintenance of pluripotency and esophageal epithelial development, and that it was preferentially expressed in ESCC (13).…”

<b>Podoplanin expression is correlated with the prognosis of lung squamous cell car</b><b>cinoma </b>

“…This is the first report to clarify the relationship between podoplanin membrane expression and clinicopathological factors. Shimada et al reported that positive podoplanin expression was significantly correlated with better prognosis of lung SqCC (24). Using immunohistolung SqCC (HR, 2.830; 95% CI, 1.456-5.500, P = 0.002) ( Table 2).…”

“…Strong podoplanin expression was significantly correlated with peripheral type (P < 0.001), with a correlation coefficient of 0.678. Recently, podoplanin has been considered as one of the candidate markers of cancer stem cells, associated with cancer cell invasion or migration, as well as the prognosis of several cancers (12,24,28,29,33). Several studies have clarified that podoplanin expression promotes epithelial-to-mesenchymal transition in morphogenetic processes.…”

Podoplanin Expression in Cancer-associated Fibroblasts Predicts Poor Prognosis in Patients with Squamous Cell Carcinoma of the Lung

“…Lymphatic vessel density examined using an antibody to podoplanin has been reported to be a prognostic factor in lung cancer (4)(5)(6). Podoplanin is also expressed in tumor cells in lung cancer (7)(8)(9)(10)(11), and is considered to regulate tumor progression and metastasis through various mechanisms, including epithelial-mesenchymal transition and platelet aggregation (12)(13)(14). Several previous studies reported that podoplanin expression in tumor cells in lung SCC was correlated with a lower incidence of lymph node metastasis and good prognosis (7)(8)(9)(10), whereas another study reported that it was associated with poor prognosis (11).…”

“…Podoplanin is also expressed in tumor cells in lung cancer (7)(8)(9)(10)(11), and is considered to regulate tumor progression and metastasis through various mechanisms, including epithelial-mesenchymal transition and platelet aggregation (12)(13)(14). Several previous studies reported that podoplanin expression in tumor cells in lung SCC was correlated with a lower incidence of lymph node metastasis and good prognosis (7)(8)(9)(10), whereas another study reported that it was associated with poor prognosis (11). Highpodoplanin expression is also observed in stromal fibroblasts, or so-called cancer-associated fibroblasts (CAFs), in lung adenocarcinoma and SCC, which has been shown to be unfavorable prognostic factor (15,16).…”