Histological and molecular aspects of oral squamous cell carcinoma (Review)

Abstract

Oral squamous cell carcinoma (OSCC) represents 95% of all forms of head and neck cancer, and over the last decade its incidence has increased by 50%. Oral carcinogenesis is a multistage process, which simultaneously involves precancerous lesions, invasion and metastasis. Degradation of the cell cycle and the proliferation of malignant cells results in the loss of control mechanisms that ensure the normal function of tissues. The aim of the current review is to present the histopathological features of OSCC, including potentially malignant changes, the international classification of tumors, the tumor invasion front and tumor biomarkers (Ki-67, p53, homeobox genes and collagen type IV), as well as the tumor microenvironment and function of cancer-associated fibroblasts in the most common type of oral cancer that is encountered by dental surgeons. In OSCC, associations have been identified between the proliferation, basal lamina degradation and connective tissue modulation. Therefore, the comparison of these factors with the survival time of OSCC patients from the histopathological diagnosis is of interest.

Keywords: Ki-67; collagen type IV; mouth neoplasms; oral cancer; oral squamous cell carcinoma; p53.

Figure 1

(A) Oral squamous cell carcinoma (OSCC) of the lateral edge of the tongue (13). (B) Severe dysplasia of the surface epithelium associated with chronic inflammatory infiltration at the stromal-epithelial interface of the dysplastic epithelium (stain, H&E; magnification, ×50) (13). Histological grades of tumor differentiation of OSCC: (C) Well-differentiated, hyperkeratosis and inflammation associated with the stromal-epithelial interface; (D) moderately differentiated; and (E) undifferentiated infiltrating and dispersed cells with no clear demarcation between the front and surrounding tissue invasion (stain, H&E; magnification, ×25) (13). Different patterns of invasion at the tumor invasion front according to the cell morphology: (F) Wide fronts of invasion (score 1); (G) islet cell widths (score 1); (H) thin infiltrating cords (score 2); and (I) individual cells invading the interface (score 3) (1). OSCC patients (J) with recurrence and (K) without recurrence. Antibody staining for Ki-67 with a high degree of nuclear staining (magnification, ×400) (16). Representative samples of homeobox protein, HOXB7 immunohistochemical expression in OSCC with (L) high and (M) low expression (32). (N) Immunohistochemical expression of type IV collagen α2 chain in undifferentiated OSCC (38).

Figure 2

In the tumoral microenvironment (TME), different stromal cells, as well as tumor cells were observed, including vascular and lymphatic endothelial cells, and pericyte support fibroblast innate and adaptive immune cells. Furthermore, the TME contained no cellular components, including the extracellular matrix, growth factors, proteases, protease inhibitors or other signaling molecules that are significant in the reactions of the stroma in the TME (4).