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.

Reduction of syndecan-1 expression during lip carcinogenesis.

BACKGROUND: Actinic cheilitis (AC) is an oral pre-cancerous lesion that sometimes develops into lip squamous cell carcinoma (SCC). Syndecan-1, a transmembrane heparan sulfate proteoglycan, modulates cell-proliferation, adhesion, migration and angiogenesis. Malignant epithelial cells often down-regulate their own syndecan-1 production, and are capable of inducing aberrant syndecan-1 expression in stromal cells. The aim of this study was to evaluate the variations in syndecan-1 expression during lip carcinogenesis, in normal lip (NL), AC and well-differentiated lip SCC. METHODS: Biopsies of NL vermillion (n = 19), AC (n = 23) and lip SCC (n = 24) were stained immunohistochemically for syndecan-1. RESULTS: Syndecan-1 expression was significantly reduced in AC and lip SCC as compared to NL (P < 0.05), with a significant reduction in lip SCC as compared to AC (P < 0.0001). In lip SCC lesions, syndecan-1 expression at the epithelium overlying the tumor was increased when compared to the tumor itself (P < 0.03), but was significantly reduced as compared to AC and NL (P < 0.001). CONCLUSION: The results showed that epithelial syndecan-1 expression is reduced as lip carcinogenesis progresses (NL>AC>lip SCC), suggesting that syndecan-1 could be a useful marker of malignant transformation in the lip.

Characterization of mast cell subpopulations in lip cancer.

BACKGROUND: Lip squamous cell carcinoma (SCC) is the most common form of oral cancer. Human mast cells (MCs), which are increased in lip SCC, are classified by their protease content in tryptase-positive (MC(T)) and tryptase/chymase-positive (MC(TC)). MC proteases are associated with tumor progression and angiogenesis. The aim of this study was to quantify and characterize MC subpopulations in lip SCC. METHODS: Serial sections from lip SCC (n = 21) and normal lip vermilion (n = 8) biopsies were stained immunohistochemically for tryptase and enzymehistochemically for chymase to determine MC subpopulation density and distribution. RESULTS: MC(T) and MC(TC) were increased in lip SCC when compared with normal lip (P < 0.0001), where MC(T) predominated over MC(TC) (P < 0.01). In lip SCC neither subpopulation predominated. Regarding distribution, MC(T) were higher than MC(TC) at the intratumoral stroma, whereas MC(TC) were higher than MC(T) at the peritumoral stroma (P < 0.01). CONCLUSIONS: The results suggest that MC subpopulations may contribute to lip SCC progression. While intratumoral MC(T) may stimulate angiogenesis, peritumoral MC(TC) may promote extracellular matrix degradation and tumor progression at the invasion front.

Increased mast cell density and protease content in actinic cheilitis.

BACKGROUND: Actinic cheilitis (AC) is a pre-malignant lesion caused by ultraviolet (UV) radiation and characterized by epithelial and connective tissue alterations. Mast cells (MCs), key contributors to solar elastosis in murine UV-irradiated skin, were characterized in order to assess their potential contribution to connective tissue degeneration in AC. METHODS: Actinic cheilitis (n = 15) and normal lip (n = 8) biopsies were stained immunohistochemically for tryptase and enzymehistochemically for chymase to determine MC density and protease content. MC subpopulations (i.e. MC(T) containing only tryptase, and MC(TC) containing chymase and tryptase) and their distribution were also determined. RESULTS: Mast cells and their proteases were increased in AC as compared with normal lip (P < 0.0001), and appeared degranulated especially around elastotic areas. MC(T) predominated over MC(TC) in AC and normal lip (P < 0.05). However, in AC MC(T) were increased in the epithelium/connective junction and connective area (P < 0.05), while in normal lip MC(T) predominated in connective and submucosal areas (P < 0.05). CONCLUSION: The results suggest that increased MC density and protease content may contribute to elastosis formation in AC. In addition, changes in MC(T) distribution may favor AC malignization.

Suppressed responsiveness to gonadotropin-releasing hormone in girls with unsustained isosexual precocity.

Eleven girls, ages 10/12 to 76/12 years, were evaluated because of early and rapid breast development. Initial clinical presentations and serum gonadotropin or estradiol determinations did not differentiate patient types. However, patients could be divided into two groups based on their responses to synthetic gonadotropin-releasing hormone: Group A consisted of seven girls with suppressed or prepubertail-type responses, and Group B consisted of four girls with pubertal or adult-type responses. Subsequent evaluation revealed that Group A patients had intermittent or unsustained isosexual precocity, whereas Group B patients had isiopathic prococious puberty. During initial evaluation, increased serum or urinary estrogen values were noted in ten of ten patients who were studied. The greatest serum E2 values (162 and 117 pg/ml) were noted in two Group A patients; three months and two years later, those patients had normal prepubertal responses to GnRH and serum E2 values of less than 4 and 14 pg/ml, respectively. Unsustained sexual precocoity in girls may be secondary to autonomous ovarian production of estrogens, and the GnRH test may be useful in evaluation of girls with isosexual precocity.