Cancer-associated fibroblasts are an infrequent finding in the microenvironment of proliferative verrucous leukoplakia-associated squamous cell carcinoma.
BACKGROUND
Cancer-associated fibroblasts (CAFs) are generally associated with negative prognostic factors. This study compares the clinicopathologic impact of CAFs in oral squamous cell carcinoma in patients with a history of proliferative verrucous leukoplakia (p-scca) and patients with conventional squamous cell carcinoma of the buccal mucosa, gingiva, and palate (c-scca).


METHODS
A retrospective clinicopathologic and immunohistochemical analysis of 97 tumor specimens from 78 patients (13 patients with proliferative verrucous leukoplakia-associated squamous cell carcinoma (n = 32) and conventional squamous cell carcinoma from the buccal mucosa, gingiva, and palate (n = 65) was conducted. Immunostaining with anti-alpha-smooth muscle actin (α-SMA) antibody was used to evaluate the presence of CAFs.


RESULTS
α-SMA expression was an infrequent finding in p-scca and seen in only 6% of p-scca compared to 40% of c-scca (P < 0.0004). In the c-scca subgroup, α-SMA significantly correlated with tumor size (T) (P = 0.009), tumor thickness (P < 0.0009), perineural invasion (P = 0.009), and microscopic grade (P = 0.018).


CONCLUSIONS
The presence of CAFs was an infrequent finding in our p-scca cohort which may contribute to its seemingly slower growing and less invasive growth pattern. In the cohort of c-scca patients, higher levels of CAFs correlated with microscopic invasiveness, tumor size, and perineural invasion. Practically, these are important observations as targeting strategies are being developed to combat carcinoma types where CAFs significance has been validated.
Department of Oral and Maxillofacial Surgery, Rambam Medical Center, Bat Galim, Haifa, Israel.|Department of Pathology, Rambam Medical Center, Bat Galim, Haifa, Israel.|Technion School of Medicine, Bat Galim, Haifa, Israel.|Department of Oral Pathology and Oral Medicine, Tel Aviv University School of Dentistry, Ramat Aviv, Tel Aviv, Israel.
Sharon J
SJ
Akrish
Department of Oral and Maxillofacial Surgery, Rambam Medical Center, Bat Galim, Haifa, Israel.|Technion School of Medicine, Bat Galim, Haifa, Israel.
Adi
A
Rachmiel
Department of Pathology, Rambam Medical Center, Bat Galim, Haifa, Israel.|Technion School of Medicine, Bat Galim, Haifa, Israel.
Edmond
E
Sabo
Department of Oral Pathology and Oral Medicine, Tel Aviv University School of Dentistry, Ramat Aviv, Tel Aviv, Israel.
Marilena
M
Vered
Department of Pathology, Rambam Medical Center, Bat Galim, Haifa, Israel.|Technion School of Medicine, Bat Galim, Haifa, Israel.
Ofer
O
Ben-Izhak
D000368:Aged; D000072645:Cancer-Associated Fibroblasts / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D005260:Female; D005881:Gingiva / Q000473:pathology; D006801:Humans; D007972:Leukoplakia, Oral / Q000473:pathology*; D008297:Male; D009061:Mouth Mucosa / Q000473:pathology; D009062:Mouth Neoplasms / Q000473:pathology*; D010159:Palate / Q000473:pathology; D012189:Retrospective Studies; D059016:Tumor Microenvironment
alpha-smooth muscle actin; cancer-associated fibroblasts; microenvironment; oral squamous cell carcinoma; proliferative verrucous leukoplakia