الفهرس 
Basal cell carcinomaOnly 14 pages are availabe for public view
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Abstract
BCC and SCC are the common malignant neoplasms of the skin. BCC is characterized by local invasion and contiguous spread. SCC is a biologically aggressive tumor and usually metastasize. Following local invasion and tissue destruction, SCC commonly metastasizes to lymph nodes.Aquaporin-3 (AQP3) is the predominant aquaporin in mammalian skin. It is an aquaglyceroporin and is capable of transporting water, glycerol, urea and hydrogen peroxide. The functions of AQP3 in skin are mostly concluded from studies in AQP3-deficient mice. AQP3-mediated glycerol transport plays an important role in stratum corneum hydration, skin elasticity, barrier recovery, wound healing and cell proliferation. It plays an important role in tumorigenesis . AQP3 was reported to mediate hydrogen peroxide uptake which was responsible for regulation of T-cell migration and cutaneous immune response.This work aimed at evaluation of the possible role of AQP3 in NMSC pathogenesis through its immunohistochemical expression in skin biopsies of these diseases and correlating this expression with the clinico-pathological parameters of the studied cases.This prospective and retrospective case - control study included 60 patients. These included 30 cases with BCC and 30 cases with SCC. Control group included 40 healthy subjects and 30 subjects with psoriasis. Cases of BCC, SCC, and psoriasis were selected from Dermatology Outpatient Clinic, Menoufia University Hospital during the period from December 2012 to May 2014. For the retrospective part of the study, tissue blocks of archived cases in Pathology Department were used. Normal skin samples were obtained from subjects attending Plastic Surgery Department.A written consent form approved by the Committee of Human Rights in Research in Menoufia University was obtained from every subject before the study initiation.All patients were subjected to detailed history taking and dermatological examination. Biopsies were taken from all cases and control subjects. Routine histopathological examination with H&E stain was done as well as immunohistochemical staining to evaluate the expression of AQP3 antigen by using Rabbit polyclonal antibody.BCC cases were 18 (60%) males and 12 (40%) females with a M: F ratio of 3:2. Their ages ranged from 12 to 75 years (ys) with 56.8 ±16.29 ys and 60 ys as mean and median values respectively. All BCC cases (100%) had lesions on the head .Histopathologically 18 cases (60%) had solid BCC ,10 cases (33.3%) had adenoid BCC and 2 cases (6.7%) had basosquamous type. Ten cases (41.7%) had free surgical margin and 14 cases (58.3 %) had involved surgical margin.SCC cases were 24 (80%) males and 6 (20%) females with a M: F ratio of 4: 1. Their ages ranged from 7 to 80 years with 45.20 ±26.15 ys and 51 ys as mean and median values respectively.Twenty cases (66.7 %) had lesions on the head and 10 cases (33.3 %) on the limbs. Histopathologically, 12 cases (40%) were grade I, 18 cases (60%) were grade II.16 cases (61.5%) had free surgical margin and10 cases (38.5 %) had involved surgical margin.All control subjects (normal skin biopsies and patients with psoriasis as an example of benign hyper proliferative skin diseases) showed positive AQP3 immunoreactivity . All normal skin sections showed membranous pattern . Psoriasis cases had 20 cases (66.7%) with cytoplasmic pattern, 2 cases (6.7%) with membranous pattern and 8 cases (26.7%) with membrano-cytoplasmic pattern.AQP3 was expressed in overlying epidermis in 80 % of BCC and SCC cases. It was expressed in tumor masses in 66.7% and 93.3% of BCC and SCC cases respectively. All positive SCC cases had membranous pattern in the overlying epidermis and tumor islands . All positive BCC cases had membranous pattern in the overlying epidermis and membrano- cytoplasmic pattern in tumor masses. Stromal positivity was detected in 86.7 % and 80 % of BCC cases and SCC cases respectively.Comparing BCC and SCC cases showed that the higher AQP3 expression percentage (P=0.03) and higher H score value (P=0.005) were significantly associated with BCC in the overlying normal epidermis compared to SCC .In tumor islands, AQP3 expression (P= 0.01) and expression percentage (P= 0.01) and higher H score (P=0.04) were significantly associated with SCC cases.BCC showed significantly higher adenexal (P<0.001), inflammatory cells (P= 0.02) and endothelial (P< 0.0001) immunoreactivity compared to SCC Normal epidermis showed significantly higher AQP3 expression (P1= 0.005), expression percentage (P1 <0.001) and H score values (P1= 0.04) compared to BCC overlying epidermis and it showed significantly higher AQP3 expression (P2<0.001), expression percentage (P2=0.001) and H score values (P2<0.001) compared to BCC tumor islands. BCC showed significantly higher endothelial (P=0.01) and inflammatory cells (P= P<0.0001) immunoreactivity compared to normal epidermis . Psoriasis showed significantly higher AQP3 expression (P1 <0.001) compared to BCC overlying epidermis and it showed significantly higher AQP3 expression (P2<0.001) expression percentage (P2=0.001) and H score values (P2<0.001) compared to BCC tumor islands.Normal epidermis showed significantly higher AQP3 expression (P1= 0.005), expression percentage (P1 <0.001) and H score values (P1 <0.001) compared to SCC overlying epidermis and it showed significantly higher AQP3 expression percentage (P2<0.001) and H score values (P2<0.001) compared to SCC tumor islands.Psoriasis showed significantly higher AQP3 expression (P1 <0.001) and and H score values (P1=0.045) compared to SCC overlying epidermis and it showed significantly higher AQP3 expression (P2<0.001), expression percentage (P2=0.001) and H score values (P2=0.001) compared to SCC tumor islands.AQP3 expression in BCC and SCC tumor islands was downregulated compared to normal and psoriatic epidermis.Comparing NMSC cases and normal epidermis showed that the higher expression (P= 0.001) and expression percentage (P<0.001) and higher H score (P<0.001)) were significantly associated with normal epidermis compared to NMSC overlying epidermis and tumor islands.Comparing NMSC cases and psoriasis showed that the higher expression (P1<0.001) was significantly associated with psoriasis compared to NMSC overlying epidermis. Higher expression (P2<0.001) and expression percentage (P2<0.001) and higher H score (P2= 0.001) were significantly associated with psoriasis compared to NMSC tumor islands.Higher H score value of BCC overlying epidermis was significantly associated with solid type (P = 0.01) and involved surgical margin (P = 0.002). Higher H score values in BCC tumor islands were significantly associated with male gender (P = 0.02) and with nodular lesions (P< 0.001). Higher H score values in SCC tumor islands were significantly associated with grade II tumors (P=0.04).Higher postivity of the BCC overlying epidermis was significantly associated with solid BCC cases (P = 0.01) . Higher postivity in BCC tumor islands was significantly associated with mixed infammatory and desmoplastic stromal type (P = 0.008) . Higher postivity in BCC stroma was significantly associated with young ages (P = 0.001) and mixed infammatory and desmoplastic stromal type (P<0.001).Comparison between positive and negative immunoreactivity of AQP3in SCC stroma showed a significant association with SCC grade II tumors (P = 0.002) and involved surgical margin (P = 0.006).The intensity of staining of AQP3 in BCC and SCC cases in comparison to the clinicopathological variables showed a statistically insignificant difference. In conclusion, AQP3 may play a role in NMSC pathogenesis. This probably occurs through aquaporin-mediated glycerol transport and ATP generation. The downregulation, observed in the current work, is mostly a result of excessive proliferation. Further studies are needed to investigate the therapeutic effect of AQP3 inhibition in NMSC treatment.