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Proteomic Profiles of Vulvar Squamous Cell Carcinoma Variants
Author(s) -
Holthoff Emily R,
Byrum Stephanie,
Kelly Thomas,
Tackett Alan,
Quick Charles M,
Post Steven R
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1081.1
Subject(s) - stroma , pathology , stromal cell , perineural invasion , metastasis , lymph node , vulvar neoplasm , medicine , biology , cancer research , carcinoma , cancer , immunohistochemistry
Vulvar squamous cell carcinoma (vSCC) is a gynecologic malignancy diagnosed in nearly 4500 women in the US each year. High risk of recurrence and nodal metastasis lead to increased morbidity and mortality in these patients. In previous studies, we identified 2 major variants of vSCC. Some tumors exhibit a pushing invasive pattern and lymphoplasmacytic (LPC) stromal response; others display an infiltrative invasive pattern and a fibromyxoid (FMX) stromal response. We also showed that infiltrative tumors with FMX stroma are more likely to recur and metastasize to the lymph nodes, contain perineural invasion, and undergo an epithelial mesenchymal transition (EMT). Molecular tumor features that contribute to these outcomes have not been well defined in vSCC and may be due to differential expression of key proteins involved in biological processes that aid in tumor growth and invasion. In this study, label‐free high resolution LC‐MS/MS was used to determine the proteomic profiles of FFPE tissue sections from 10 infiltrative vSCC with FMX stroma and 10 pushing vSCC with LPC stroma. Of these 20 tumors, 11 were associated with recurrence and 8 contained lymph node metastases. Proteomic profiles were associated with morphologic tumor features, tumor recurrence, and nodal metastases to identify proteins linked to increased risk of adverse outcomes. When comparing infiltrative and pushing tumors, 205 proteins exhibited significant expression changes between the two groups. Importantly, 42 proteins were uniquely identified in infiltrative tumors. Included in these was thrombospondin‐4, a glycoprotein that mediates cell‐matrix interactions and may play a role in macrophage recruitment. In addition, 96 proteins were identified only in the pushing tumors, including STAT1, which may play a significant role in mediating effects of the inflammatory stromal response through IFNγ signaling. Expression of 105 proteins was either significantly different or uniquely identified in recurrent tumors, and the expression of 115 proteins was either uniquely identified or significantly varied in tumors with nodal metastases. Included in these 115 significant proteins was SRPX2, an important regulator of FAK signaling and cell motility, which could contribute to increased metastatic potential in these tumors. Overall, our results identify a proteomic profile in vSCC that implicates a role for specific pathways in differentiating aggressive vulvar squamous cell carcinoma as defined by morphologic tumor features, recurrence, and nodal metastases. Support or Funding Information UAMS TRI grants UL1TR000039 and KL2TR000063; SPaT institutional training grant T32GM106999