SERPINE1 and SMA expression at the invasive front predict extracapsular spread and survival in oral squamous cell carcinoma

Abstract

Background:Extracapsular spread (ECS) in cervical lymph nodes is the single-most prognostic clinical variable in oral squamous cell carcinoma (OSCC), but diagnosis is possible only after histopathological examination. A promising biomarker in the primary tumour, alpha smooth muscle actin (SMA) has been shown to be highly prognostic, however, validated biomarkers to predict ECS prior to primary treatment are not yet available.Methods:In 102 OSCC cases, conventional imaging was compared with pTNM staging. SERPINE1, identified from expression microarray of primary tumours as a potential biomarker for ECS, was validated through mRNA expression, and by immunohistochemistry (IHC) on a tissue microarray from the same cohort. Similarly, expression of SMA was also compared with its association with ECS and survival. Expression was analysed separately in the tumour centre and advancing front; and prognostic capability determined using Kaplan–Meier survival analysis.Results:Immunohistochemistry indicated that both SERPINE1 and SMA expression at the tumour-advancing front were significantly associated with ECS (P<0.001). ECS was associated with expression of either or both proteins in all cases. SMA+/SERPINE1+ expression in combination was highly significantly associated with poor survival (P<0.001). MRI showed poor sensitivity for detection of nodal metastasis (56%) and ECS (7%). Both separately, and in combination, SERPINE1 and SMA were superior to MRI for the detection of ECS (sensitivity: SERPINE1: 95% SMA: 82% combination: 81%).Conclusion:A combination of SMA and SERPINE1 IHC offer potential as prognostic biomarkers in OSCC. Our findings suggest that biomarkers at the invasive front are likely to be necessary in prediction of ECS or in therapeutic stratification.

Malignant peripheral nerve sheath tumor (MPNST) in the spine: a retrospective analysis of clinical and molecular prognostic factors

“…Meanwhile, we found that Ki67 LI was significantly higher in high grade MPNSTs than that in low grade ones, probably suggesting that Ki67 could help distinguish between high and low grade MPNSTs. Both SMA and CD57 were confirmed to be the prognostic factors in some other tumors [33][34][35] but rarely reported in MPNSTs. We confirmed that both SMA and CD57 were not independent factors for postoperative recurrence and overall survival.…”

Oral cancer‐associated fibroblasts predict poor survival: Systematic review and meta‐analysis

“…After title/abstract screening, 20 text articles were subjected for full‐text evaluation, out of which nine were excluded for the following reasons: cases of OSCC not limited to the oral cavity (Parajuli et al, ), no Kaplan–Meier survival plots (Fonseca et al, ; Kellermann et al, , ; Lim et al, ; Vered, Dayan, et al, ; Zhou et al, ), immunohistochemical staining for the identification of CAFs other than α‐SMA (Inoue et al, ), and missing data (i.e., CAF density, mean age of patients and gender classification) (Inoue et al, ; Sobral et al, ). Finally, 11 articles were included in the meta‐analysis (Bae et al, ; Bello et al, ; Dayan et al, ; Dhanda et al, ; Ding et al, ; Fujii et al, ; Kawashiri et al, ; Li et al, ; Marsh et al, ; Matsuoka et al, ; Vered, Dobriyan, et al, ) (Table ; Figure ).…”

Secretome profiling of oral squamous cell carcinoma-associated fibroblasts reveals organization and disassembly of extracellular matrix and collagen metabolic process signatures

“…Possible mechanisms by which SERPINE1 contributes to cancer dissemination include the prevention of excessive degradation of the extracellular matrix, modulation of cell adhesion, and stimulation of angiogenesis and cell proliferation [38][39][40]. Immunohistochemical analysis revealed that both SERPINE1 and α-SMA at the tumor-advancing front of OSCCs were significantly associated with extracapsular spread of cervical lymph nodes, a prognostic marker of OSCC outcome, and the combination of α-SMA/SERPINE1 positivity was significantly associated with poor survival of OSCC patients [41]. Interestingly, C-188-9, a STAT-3 inhibitor, decreased pulmonary fibrosis and resulted in inhibition of fibroblast-to-myofibroblast differentiation and TGF-β-induced expression of multiple genes including SERPINE1 [42].…”