scholarly journals Perineural Invasion Correlates With Common Pathological Variables and Clinical Outcomes of Patients With Squamous Cell Carcinoma of the Vulva Treated With Primary Radical Surgery and Inguinal-femoral Lymphadenectomy

In Vivo ◽  
2021 ◽  
Vol 35 (2) ◽  
pp. 1051-1056
Author(s):  
ANGIOLO GADDUCCI ◽  
SABINA PISTOLESI ◽  
STEFANIA COSIO ◽  
CHIARA COMUNALE ◽  
ANTONIO FANUCCHI ◽  
...  
PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0241551
Author(s):  
Aaron Chen ◽  
Alexis L. Santana ◽  
Nicole Doudican ◽  
Nazanin Roudiani ◽  
Kristian Laursen ◽  
...  

Perineural invasion is a pathologic process of neoplastic dissemination along and invading into the nerves. Perineural invasion is associated with aggressive disease and a greater likelihood of poor outcomes. In this study, 3 of 9 patients with cutaneous squamous cell carcinoma and perineural invasion exhibited poor clinical outcomes. Tumors from these patients expressed high levels of MAGE-A3, a cancer testis antigen that may contribute to key processes of tumor development. In addition to perineural invasion, the tumors exhibited poor differentiation and deep invasion and were subsequently classified as Brigham and Women’s Hospital tumor stage 3. Cyclin E, A and B mRNA levels were increased in these tumors compared with normal skin tissues (102.93±15.03 vs. 27.15±4.59, 36.83±19.41 vs. 11.59±5.83, 343.77±86.49 vs. 95.65±29.25, respectively; p<0.05). A431 cutaneous squamous cell carcinoma cells pretreated with MAGE-A3 antibody exhibited a decreased percentage S-phase cells (14.13±2.8% vs. 33.97±1.1%; p<0.05) and reduced closure in scratch assays (43.88±5.49% vs. 61.17±3.97%; p = 0.0058). In a syngeneic animal model of squamous cell carcinoma, immunoblots revealed overexpression of MAGE-A3 and cyclin E, A, and B protein in tumors at 6 weeks. However, knockout of MAGE-A3 expression caused a reduction in tumor growth (mean tumor volume 155.3 mm3 vs. 3.2 mm3) compared with parental cells. These results suggest that MAGE-A3 is a key mediator in cancer progression. Moreover, elevated collagen XI and matrix metalloproteases 3, 10, 11, and 13 mRNA levels were observed in poorly differentiated cutaneous squamous cell carcinoma with perineural invasion compared with normal skin tissue (1132.56±882.7 vs. 107.62±183.62, 1118.15±1109.49 vs. 9.5±5, 2603.87±2385.26 vs. 5.29±3, 957.95±627.14 vs. 400.42±967.66, 1149.13±832.18 vs. 19.41±35.62, respectively; p<0.05). In summary, this study highlights the potential prognostic value of MAGE-A3 in clinical outcomes of cutaneous squamous cell carcinoma patients.


Background: The objective of surgical management of oral squamous cell carcinoma (OSCC) is adequate resection with a clear margin. However, there is still a debate as to the optimal length for a mandibular resected margin. Objective: To examine the length of peri-neural spreading in T4 mandibular invaded oral cavity squamous cell carcinoma. Materials and Methods: Twenty-eight T4 pathological OSCC specimens that involved mandible and serial slices were studied and the length of tumor spreading along the inferior alveolar nerve (IAN) was determined. Tumor characteristics, risk factors, and survival were analyzed. Results: The incidence of peri-neural invasion was 11.11%, and IAN invasion was found in 14.29% of the tumor-invaded mandibular marrow. The length of tumor spreading along IAN was 3 to 12 mm. Poor prognostic factors of T4 OSCC were it being located on the tongue (HR 14.16), was pathological N2-3 (HR 31.05), and had high-risk features such as peri-neural invasion, lymphovascular invasion, and extra-nodal extension. Conclusion: A mandibular resected margin of at least 18 mm is recommended as a clear surgical margin in cases of T4 mandibular invasion OSCC. Keywords: Oral cancer, Perineural invasion, Inferior alveolar nerve, Squamous cell carcinoma, Mandibulectomy


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