Differential senescence capacities in meibomian gland carcinoma and basal cell carcinoma

Abstract

Meibomian gland carcinoma (MGC) and basal cell carcinoma (BCC) are common eyelid carcinomas that exhibit highly dissimilar degrees of proliferation and prognoses. We address here the question of the differential mechanisms between these two eyelid cancers that explain their different outcome. A total of 102 confirmed MGC and 175 diagnosed BCC cases were analyzed. Twenty confirmed MGC and twenty diagnosed BCC cases were collected to determine the telomere length, the presence of senescent cells, and the expression levels of the telomere capping shelterin complex, P53, and the E3 ubiquitin ligase Siah1. Decreased protein levels of the shelterin subunits, shortened telomere length, over-expressed Ki-67, and Bcl2 as well as mutations in P53 were detected both in MGC and BCC. It suggests that the decreased protein levels of the shelterin complex and the shortened telomere length contribute to the tumorigenesis of MGC and BCC. However, several parameters distinguish MGC from BCC samples: (i) the mRNA level of the shelterin subunits decreased in MGC but it increased in BCC; (ii) P53 was more highly mutated in MGC; (iii) Siah1 mRNA was over-expressed in BCC; (iv) BCC samples contain a higher level of senescent cells; (v) Ki-67 and Bcl2 expression were lower in BCC. These results support a model where a preserved P53 checkpoint in BCC leads to cellular senescence and reduced tumor proliferation as compared to MGC.Basal cell carcinoma (BCC) and meibomian gland carcinoma (MGC), which is also referred to as ocular sebaceous carcinoma, are among the most common eyelid carcinomas in the world. However they exhibit very different levels of proliferation and prognosis. MGC represents 5% of all malignant eyelid tumors, whereas BCC accounts for 90% of these malignancies.1 BCC is a locally invasive and curable cancer of epidermal basal cells that rarely spreads beyond the original tumor site. Compared with BCC, MGC is a life-threatening neoplasm that represents a challenge to ophthalmologists and pathologists due to its frequent recurrence and metastasis.2 MGC is often misdiagnosed for years in the clinic as an inflammatory condition and is infrequently biopsied or pathologically diagnosed until it appears to exhibit invasive infiltration. The delay in the correct diagnosis of MGC

Periocular basal cell carcinoma - clinical perspectives

“…42 It was found that telomere length was shortened and gene expression correlated with cell proliferation (Bcl-2, Ki-67) was increased in BCC. 43…”

Ocular basal cell carcinoma: a brief literature review of clinical diagnosis and treatment

“…Margin control is strongly recommended for cases treated with local excision. Initial treatment with local excision or MMS should achieve negative resection margins in order to reduce the risk of local recurrence 18. Treatment needs to be individualized to the patient situation, tumor characteristics and histological subtype.…”

Glucocorticoids delay RAF-induced senescence promoted by EGR1

“…In both cases, senescence evasion may to be required for cancer progression, as has been reported for head and neck squamous cell carcinoma (Bian et al, 2012). Loss of heterozygosity of PTCH1, which is frequent in basal cell carcinoma and in SHH cerebellum medulloblastoma, has been shown to trigger senescence in preneoplastic medulloblastoma lesions (Tamayo-Orrego et al, 2016), and senescence features have been reported in basal cell carcinoma (Hida et al, 2009;Zhang et al, 2016). Hence, in addition to weakening immune surveillance of cancer, glucocorticoids could participate in senescence evasion.…”