Study on Tumor Budding and Immunoexpression of Cancer Stem Cell Marker ALDH1 in Oral Squamous Cell Carcinoma.

Background Tumor budding refers to the presence of individual cancer cells or small clusters of cells that break away from the main tumor and are seen at the edge where the tumor is invading surrounding tissue. Aldehyde dehydrogenase 1 is a cancer stem cell marker that causes oxidation of retinol to retinoic acid in early stem cell differentiation. This study aimed to examine tumor budding in oral squamous cell carcinoma and explore how it relates to various clinical and pathological factors. A study of cancer stem cell marker ALDH1 was also done with correlation to tumor budding and prognostic markers. Material and methods A prospective study was carried out in a pathology department over one year and included all newly diagnosed cases of oral squamous cell carcinoma that had undergone surgical resection. Both the gross specimens and the tissue sections stained with hematoxylin and eosin (H&E) from paraffin-embedded samples were examined for tumor size, histopathological grade, in situ carcinoma, necrosis, lymphovascular emboli, perineurial invasion, and lymph node metastasis. Tumor budding was evaluated for every case by observing tumor buds (clusters of a single tumor cell or a small cluster of tumor cells (<5) at the invasive front of the tumor) at 40x. Immunohistochemical analysis for ALDH-1 was performed on paraffin-embedded histopathological sections. Results A total of 50 cases were included in the study, with a mean age of 49 years and a male-to-female ratio of 7.3:1. The most common site of carcinoma was buccal mucosa (34%), followed by tongue (30%). Ninety percent (90%) of cases were moderately differentiated squamous cell carcinoma, with 82% of cases showing lymphovascular emboli and 32% showing perineural invasion. The highest number of cases, 22% (11), were classified as pT4aN0Mx, followed by 16% (8 cases each) classified as pT2N0Mx and pT3N0Mx. Sixty-six percent (66%; n=33) of cases showed high-grade tumor budding while 34% (n=17) showed low-grade tumor budding. Eighty-eight point eight percent (88.8%; n=32) of cases with high-grade tumor budding as well as lymphovascular invasion were observed with a statistically significant association (p=0.042). The study found a statistically significant link between high-grade tumor budding and the presence of lymph node metastasis (p=0.003). Fifty-eight percent (58%) of cases showed positive immunostaining of ALDH1 with varying intensity from weak to strongly positive. ALDH1 expression showed a significant association with high-grade tumor budding, with the result being statistically highly significant (p = 0.0001). Conclusion High-grade tumor budding is associated with increased expression of cancer stem cell marker ALDH1 in oral squamous cell carcinoma. It is also associated with lymphovascular invasion and lymph node metastasis, suggesting a poor prognosis in these patients. It is recommended that tumor budding should be included in histopathological reports of oral carcinoma. ALDH1 may be explored as a potential target for therapy in oral carcinoma. The authors suggest that further larger studies with extended follow-up may be done to establish the role of tumor budding and ALDH1 in the prognosis of oral carcinoma.