Prognostic and Risk Factors in Patients with Locally Advanced Cutaneous Squamous Cell Carcinoma of the Trunk and Extremities

Abstract

55 patients with advanced cutaneous squamous cell carcinoma (CSCC) of the trunk and extremities were studied. A Tissue Microarray was constructed using immunohistochemistry to quantify expression of the HER family, E-cadherins, and podoplanin. Clinical and histopathological factors related to lymph node metastasis and prognosis were also established. Primary tumor positivity was 25.5% for EGFR, 87.3% for HER-3, and 48.1% for HER-4. Metastases were positive for EGFR in 41.7%, for HER-3 in 83.3%, and HER-4 in 43.5%. HER-2 was negative in all samples. Membrane E-cadherin and cytoplasmic E-cadherin were positive in 47.3% and 30.2% of primary tumors and 45.5% and 27.3% of metastases, respectively. Podoplanin was positive in 41.8% of primary tumors and 41.7% of metastases. Intratumoral lymphocytic infiltrate was associated with lymph node metastasis. Patients with T3 tumors had better cancer-specific survival (CSS) than those with T4 tumors; patients with no lymph node involvement had better CSS than patients with N1 tumors. Undifferentiated tumors and hyperexpression of podoplanin were negative prognostic indicators on multivariate analysis.

Characterisation of Prognosis and Invasion of Cutaneous Squamous Cell Carcinoma by Podoplanin and E-Cadherin Expression

“…Additionally, we noted the membranous staining being attenuated in favour of a cytoplasmic E-cadherin expression. This is in concordance with Vinicius et al [22] , who detected a cytoplasmic staining of E-cadherin in 27.3% in lymph node metastases. Membranous E-cadherin was decreased in lymph node metastases so that augmenting cytoplasmic staining might be related to tumour progression in cSCC.…”

“…However, skin and lymph node metastases did not diverge in podoplanin expression, displaying similar staining properties to the corresponding primary cSCC. This observation confirms prior analysis of Vinicius et al [22] , who detected podoplanin-staining in 41.8% of cSCC and in 41.7% of metastases, thus revealing no significant differences.…”

“…The translocation might indicate proteolysis or lysosomal degradation of E-cadherin [25] . This outcome corresponds to recent studies where cytoplasmic staining of E-cadherin was interpreted as functional loss, promoting an attenuation of cellular integrity and featuring the development of malignant transformation and metastasis in the setting of EMT [20,22,25,26] . The Kaplan-Meier analysis in order to investigate the influence of these staining characteristics to metastasis achieved no significant results.…”

In Silico Analysis Validates Proteomic Findings of Formalin-fixed Paraffin Embedded Cutaneous Squamous Cell Carcinoma Tissue

“…While the majority of patients with early cSCC have a good prognosis, outcomes for patients with metastatic disease are poor, with a 5-year survival rate of less than 10% (4,5). One of the most prominent contributing factors to poor patient outcome is the lack of sensitive biomarkers to facilitate early diagnosis and management of the tumor.…”

“…One of the most prominent contributing factors to poor patient outcome is the lack of sensitive biomarkers to facilitate early diagnosis and management of the tumor. A handful of genetic biomarkers have been studied in cSCC, including cellular tumor antigen p53 (TP53), notch 1 (NOTCH1) (6,7), human epidermal growth receptor 2 (HER2), HER4, E-cadherin (CDH1), epidermal growth factor receptor (EGFR), and podoplanin (PDPN) (5,8,9), and some have shown potential for prognostication (9)(10)(11)(12). However, there is a lack of evidence to recommend the use of these biomarkers for cSCC tumor stratification.…”