Evaluation of Patched-1 Protein Expression Level in Low Risk and High Risk Basal Cell Carcinoma Subtypes

Abstract

Objective: Basal cell carcinoma (BCC) is the most common malignancy in humans and represents a growing public health care problem. The major etiological factors contributing to BCC development are exposure to ultraviolet radiation and genetic alterations. BCC is primarily caused by dysregulation of sonic Hedgehog (HH) signaling pathway in basal cells of the skin. BCC can be classified into low risk non-aggressive and high risk aggressive subtypes. BCC subtypes differentiation is essential for prognosis and for better disease management and treatment strategies. The aim of this study was to assess the correlation between PTCH1 protein expression level and the aggressiveness of BCC histopathology. Methods: Archival paraffin embedded blocks containing BCC were retrieved from a cohort of 101 patients. Immunohistochemistry staining was performed to assess the expression level of PTCH1 which is a key component of Hedgehog pathway. Results: 101 paraffin embedded samples were evaluated and classified as high risk and low risk BCC subtypes by histopathological finding. High risk BCC subtypes were found in 40 samples (39.6%) and low risk subtypes were identified in 61 samples (60.4%). Nodular was the most frequent subtype which was found in (56/ 101), followed by infiltrative (22/101) and micronodular (14/ 101) subtypes. Positive PTCH1 expression was found highest in nodular subtypes (46.5%). Conclusion: In this study, the correlation between low risk or high risk BCC subtypes and PTCH1 expression level was not statistically significant (p>0.05), but the frequency of positive PTCH1 expression was found to be higher in low risk subtypes than high risk BCC subtypes.

Expression of Hedgehog Signaling Pathway Proteins in Basal Cell Carcinoma: Clinicopathologic Study

“… 25 Also, Almomani et al found that the correlation between low-risk or high-risk BCC subtypes and the PTCH1 expression level was not statistically significant. 26 We found that the intensity of IHC staining for PTCH1 was higher in superficial BCC than other subtypes, although this difference was not significant. We speculate that this may be related to the anatomical location of superficial BCC, where more superficial tumors have a higher mutational burden or are more likely to accumulate UV-associated mutations.…”

Does the histopathological subtype of primary basal cell carcinoma predict the subtype of secondary tumours? What role do genetic mutations play?

“…Inactivating mutations of PTCH1 and SMO, occur in 90% and 10%, respectively of basal cell carcinoma. 16 Somatic mutations arise due to the effects of ultraviolet radiation to DNA within basaloid keratinocytes.…”

“…Recent publications have tried to elucidate the genetic profiles of BCC subtypes. 16 , 25 , 26 , 27 There has been a strong association identified between expression of the PTCH1 gene in low‐risk tumours (i.e., nodular and superficial) compared to high‐risk tumours (i.e., micronodular and infiltrative), although this was not found to be statistically significant. 16 A more recent study looked specifically at low‐risk BCCs including nodular and superficial variants and found that both the NOTCH1 and PTCH1 gene were more frequent in superficial than nodular BCCs.…”

“… 16 , 25 , 26 , 27 There has been a strong association identified between expression of the PTCH1 gene in low‐risk tumours (i.e., nodular and superficial) compared to high‐risk tumours (i.e., micronodular and infiltrative), although this was not found to be statistically significant. 16 A more recent study looked specifically at low‐risk BCCs including nodular and superficial variants and found that both the NOTCH1 and PTCH1 gene were more frequent in superficial than nodular BCCs. 28 They also noted that PTCH1 mutation was significantly associated with intermittent sun exposure and the development of a single BCC, which would be consistent with nodular and superficial subtypes being the most common.…”

Recent Advances in Signaling Pathways Comprehension as Carcinogenesis Triggers in Basal Cell Carcinoma

“…Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by mutations in the patched ( PTCH ) 1 gene, PTCH2 gene and suppressor of the fused ( SUFU ) gene, which are negative regulators of the hedgehog (Hh) pathway [ 8 ]. PTCH1 , located on chromosome 9q22.3, encodes the homologous transmembrane protein PTCH1 that acts as a receptor for the Hh pathway [ 9 ]. PTCH2 is located on chromosome 1p34 and encodes for PTCH2 and SUFU is located on chromosome 10q24.32 and encodes for the suppressor of a fused homologous protein, SUFU [ 8 ].…”