Possible role of ALDH1 and CD44 in lip carcinogenesis

Abstract Lip squamous cell carcinoma (LSCC) accounts for 12% of all head and neck cancers. It is caused by chronic exposure to ultraviolet light solar radiation and related to previous actinic cheilitis (AC). This study aimed to investigate the immunostaining of the putative cancer stem cells (CSC) markers ALDH1 and CD44 in AC (n=30) and LSCC (n=20). ALDH1 positivity was found to be statistically higher in LSCC than in AC lesions (p=0.0045), whilst CD44 expression was statistically higher in AC than in LSCC lesions (p=0.0155). ALDH1+ cells in AC lesions were associated with specific clinical features: a younger age (<60 years old), the female gender, white skin, not smoking or consuming alcohol, and a fast evolution, and not associated with the chronic exposure to UV radiation (p<0.0001). CD44 positivity was associated with patients who were male, feoderm, smoked, consumed alcohol, underwent occupational exposure to UV-radiation, and demonstrated lesions with log-time evolution (p<0.0001). ALDH1 + cells were associated with mild dysplasia using a system from the World Health Organization (WHO), and with a low risk of malignant transformation, according to the binary system (p<0.0001). CD44+ cells were also associated with moderated dysplasia, according to the WHO system. In LSCC, ALDH1 + cells were positively associated with patients who were older (≥ 60 years old), smokers, and with those who consumed alcohol (p<0.0001). CD44 + cells in LSCC were associated with older (≥ 60 years old) patients as well, but also with female patients, white skin, non-smokers, and individuals who did not consume alcohol (p<0.0001), all of whom showed distinct patterns in pre- and malignant lesions of both markers. Additionally, in LSCC, both ALDH1 and CD44 staining were associated with smaller tumor sizes (T1/T2; p<0.0001). In summary, although both ALDH1 and CD44 were associated with the presence of dysplasia in AC lesions, the present findings suggest that ALDH1 and CD44 may be activated by different etiopathogenic pathways, predominantly in distinct steps of oral carcinogenesis. CD44 would thus be more significantly related to the potentially malignant lesion, while ALDH1 would be closely linked to malignancy.

Actinic Cheilitis and Lip Squamous Cell Carcinoma: Clinical and, Histopathological Aspects and p53 Protein Expression / 대한피부과학회지

BACKGROUND: Actinic cheilitis (AC) is the main precancerous lesion of the lip. Knowledge of prognostic and diagnostic markers can have positive impacts, although the exact transition rate from AC to lip squamous cell carcinoma (LSCC) is unknown. OBJECTIVE: We analyzed 59 patients to investigate the relationship between clinical and histopathological features and the expression of the p53 protein in AC and LSCC. METHODS: We retrospectively reviewed 59 patients who received biopsy for AC and LSCC between January 2005 and December 2012 and compared clinical and histopathological features of AC and LSCC. RESULTS: The ratios of males to females for AC and LSCC were 1.3:1 and 1.7:1. The mean ages of those with AC and LSCC were 66.4 and 70.1 years. All of the lesions involved the lower lip, and the most frequently affected site was the right side of the lip in LSCC. Persistent fissures with scales and exudative ulcers were noted 90.6% and 43.7% of the AC cases, respectively. The intensity of the inflammatory infiltrate was significantly associated with the degree of epithelial dysplasia. Most LSCCs (96.2%) were immunoreactive to the p53 protein. The intensities of AC and LSCC p53 protein expression were 1.1 and 2.4. The degree of epithelial dysplasia was the only histopathological finding significantly associated with p53 protein expression. CONCLUSION: An intense inflammatory infiltrate in AC was predictive of a microinvasive SCC. Therefore, p53 protein immunoreactivity may be an important indicator in lip carcinogenesis and the degree of epithelial dysplasia.

E-cadherin and c-Met expression in actinic cheilits and lip squamous cell carcinoma

Objective: The aim of this study was to assess epithelial expression of E-cadherin and c-Met in normal lip, in actinic cheilitis and lip squamous cell carcinoma. Study Design: Biopsies of normal lip vermillion (NL, n=18), actinic cheilitis (AC, n=37), and lip SCC (n=22) were processed for E-cadherin and c-Met immunodetection. Epithelial and tumor cell expression was scored for each sample considering staining intensity and percentage. Results: E-cadherin expression was significantly reduced in AC and lip SCC as compared to normal lip (P<0.05), with a significant reduction in lip SCC as compared to AC (P=0.003). Expression of c-Met was significantly higher in AC and lip SCC as compared to NL (P<0.05), with a significant increase in lip SCC as compared to AC (P<0.0001). Conclusion: The results showed that epithelial E-cadherin expression is reduced and c-Met expression is increased as lip carcinogenesis progresses, suggesting that these proteins may be useful markers of malignant transformation.

Comparative analysis of the mast cell density in normal oral mucosa, actinic cheilitis and lip squamous cell carcinoma

Previous studies have shown that the number of mast cells is increased in ultraviolet (UV) irradiated skin and in neoplasias. Actinic cheilitis (AC) is a lesion caused by excessive exposure to sunlight that can transform into lip squamous cell carcinoma. The aim of this study was to compare the number of mast cells in 4 groups: NOM = normal oral mucosa (n=6); MDAC = mild dysplasia in actinic cheilitis (n=13); SDAC = severe dysplasia in actinic cheilitis (n=13); and LSCC = lip squamous cell carcinoma (n=15). The sections were stained by histochemical technique of blue toluidine and visual counting was performed with the aid of a reticulum coupled to the microscope ocular. A calibrated observer performed the count in 5 fields by case at ×400 magnification. The largest mean number of mast cells per group was observed in LSCC (40.1), followed by MDAC (30.5), SDAC (28.6) and NOM (12.2). There were significant differences between NOM and MDAC (p<0.05) and between NOM and LSCC (p<0.05). The increased density of mast cells observed in AC and in LSCC compared to NOM suggests a role for the mast cells in the development of these lesions.

Estudos prévios mostram que os mastócitos estão significantemente aumentados na pele irradiada por ultra-violeta e neoplasias. A queilite actínica (QA) é uma lesão causada por excessiva exposição solar, que pode transformar-se em carcinoma espinocelular de lábio. O objetivo deste estudo foi comparar o número de mastócitos em 4 grupos: MON = mucosa oral normal (n=6); QADL = queilite actínica com displasia leve (n=13); QADS = queilite actínica com displasia severa (n=13); e CECL = carcinoma espinocelular de lábio (n=15). Os cortes foram corados pela técnica histoquímica do azul de toluidina e a contagem visual foi realizada utilizando um retículo acoplado à ocular do microscópio. Um observador calibrado realizou a contagem em 5 campos por caso em magnificação de ×400. A média de mastócitos por grupo foi maior no CECL (40,1), seguida da QADL (30,5), QADS (28,6) e MON (12,2). Houve diferença estatisticamente significante entre MON e QADL (p<0,05) e entre MON e CECL (p<0,05). A maior densidade de mastócitos na QA e no CECL em relação à MON sugere um papel para os mastócitos no desenvolvimento dessas lesões.