Immunohistochemical analysis of the mechanistic target of rapamycin and hypoxia signalling pathways in basal cell carcinoma and trichoepithelioma

Background: Basal cell carcinoma (BCC) is the most common cancer in Caucasians. Trichoepithelioma (TE) is a benign neoplasm that strongly resembles BCC. Both are hair follicle (HF) tumours. HFs are hypoxic microenvironments, therefore we hypothesized that hypoxia-induced signalling pathways could be involved in BCC and TE as they are in other human malignancies. Hypoxia-inducible factor 1 (HIF1) and mechanistic/mammalian target of rapamycin (mTOR) are key players in these pathways. Objectives: To determine whether HIF1/mTOR signalling is involved in BCC and TE. Methods: We used immunohistochemical staining of formalin-fixed paraffin-embedded BCC (n = 45) and TE (n = 35) samples to assess activity of HIF1, mTORC1 and their most important target genes. The percentage positive tumour cells was assessed manually in a semi-quantitative manner and categorized (0%, 80%). Results: Among 45 BCC and 35 TE examined, expression levels were respectively 81% and 57% (BNIP3), 73% and 75% (CAIX), 79% and 86% (GLUT1), 50% and 19% (HIF1 alpha), 89% and 88% (pAKT), 55% and 61% (pS6), 15% and 25% (pMTOR), 44% and 63% (PHD2) and 44% and 49% (VEGF-A). CAIX, Glut1 and PHD2 expression levels were significantly higher in TE when only samples with at least 80% expression were included. Conclusions: HIF and mTORC1 signalling seems active in both BCC and TE. There are no appreciable differences between the two with respect to pathway activity. At this moment immunohistochemical analyses of HIF, mTORC1 and their target genes does not provide a reliable diagnostic tool for the discrimination of BCC and TE

Trends in the incidence of basal cell carcinoma by histopathological subtype

Background As a result of the high prevalence, basal cell carcinoma (BCC) causes a significant and expensive health care problem. Objective In this study, we evaluate the proportional increase in BCC by histological subtype over the last two decades. Methods We retrospectively reviewed all primary histological confirmed BCCs diagnosed in the Maastricht University Medical Centre in The Netherlands in the years 1991, 1999 and 2007. Results An annual increase of the number of BCCs of 7% for both genders was shown. The age-standardized incidence rates for BCC increased between 1991 and 2007 from 54.2 to 162.1 per 100 000 men and from 61.7 to 189.8 per 100 000 women. The proportion of superficial BCC increased significantly from 17.6% to 30.7%. Conclusion The incidence of BCC is continuing to increase this century. The observed shift to the superficial histological subtype, which can be treated non-surgically, might reduce the workload in the busy dermatologists practice

Aesthetic evaluation after non-invasive treatment for superficial basal cell carcinoma

Background Cosmetic results following non-invasive treatments are difficult to compare. Although qualified objective scar assessment scales are available, they are not used in dermatological studies. Usually a 4-point scale is used in dermatological scars. The reproducibility of this method has never been evaluated. Moreover, significant specific scar characteristics are lacking. The patient and observer scar assessment scale (POSAS) is a scale qualified for the assessments of surgical scars. It has proven to be as reliable as the widely used Vancouver Scar Scale, but has the advantage that it includes the patient's opinion and specifies different scar characteristics. Objective Both methods were used to evaluate cosmetic results following non-invasive treatments of superficial basal cell carcinoma (BCC). Methods A total of 54 lesions following non-invasive treatment for BCC in 54 patients were evaluated with the traditional 4-point scale and the POSAS. Results The 4-point scale showed the best reproducibility and had an intra-class correlation coefficient (ICC) of 0.66 (95% CI: 0.520.77) for a single observer and 0.85 (95% CI: 0.770.91) for multiple observers. The ICC of the POSAS was 0.41 (95% CI: 0.210.58) for a single observer and 0.67 (95% CI: 0.450.81) for three observers. The scar characteristics, vascularity and pigmentation were most decisive for the overall opinion. Conclusion The use of the 4-point scale is a valid method to compare scars of non-invasive dermatological treatments. Supplementary registering vascularity and pigmentation can be useful in future studies