الفهرس 
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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 metastasizes. Following local invasion and tissue destruction, SCC commonly metastasizes to lymph nodes. HIF-1α is a transcriptional activator that mediates adaptive responses to hypoxia. Its activity is increased in majority of human cancers as a result of genetic alteration and intratumoral hypoxia. Previous studies detected up regulation of HIF-1α in different tumors. Proof of principle studies in mouse models suggests that inhibition of HIF-1 activity may have therapeutic effects, especially in combination with other anticancer drugs. This work aimed to investigate the role of HIF-1α in non melanoma skin cancer through its immunohistochemical localization in skin biopsies of these diseases. Furthermore, we aimed to correlate its expression with different clincopathologic parameters of the studied cases.
This prospective and retrospective case-control study included 64 subjects. These included 20 cases with BCC, 20 cases with SCC, 4 cases with SCC in situ diagnosed according to their histopathological finding and 20 age and sex matched healthy subjects as a control group. Cases of BCC and SCC were selected from Dermatology Outpatient Clinic, Menoufiya University Hospital during the period from March 2014 to March 2015. 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 HIF-1α antigen by using Rabbit polyclonal antibody.
BCC cases were 5 (25%) males and 15 (75%) females with a M: F ratio of 1:3. Their ages ranged from 50 to 87 years with 61.7±9.96 as a mean± SD value. Lesion size ranged from 0.3 to 3 cm with 1.67± 0.68 as a mean ± SD value. Regardenig the site, 17 cases were on the face (85%) and 3 were on the scalp (15%). Regarding the clinical subtypes of BCC, 18 cases (90%) were presented with ulcer and 2 case (10%) was presented with nodular lesion. Histopathologically18 cases (90%) had solid BCC, 1 case (5.0%) had adenoid BCC and 1 case (5.0%) had keratotic BCC. 8 cases (57.1%) had free surgical margin and 6 cases (42.9 %) had involved surgical margin.SCC insitu cases were all males. Age of the patients ranged from 60 to 75 years.. Regardenig the site, 3 cases (75%) were on the oral mucous membrane and 1 case (25%) was on the face. Lesion size ranged from 0.2 to1cm. Regarding the clinical presentation, 3(75%) were presented with polyps and 1 (25%) was presented with nodule.
SCC were 8 (40%) males and 12(60%) females with a M: F ratio 2:3. Their ages ranged from 38 to 81 years with 62.30±12.36 as mean± SD value. Lesion size ranged from 1 to 8 cm with 3.43±2.90 as mean ± SD value. Regardenig the site, 8 cases (40 %) were on the face, 5 cases (25 %) were on the extremeties, and 7 cases were on the vulva. Regarding the clinical types of SCC, 16 cases (80%) were presented with ulcer and 4 cases (20%) were presented with nodular lesions. Histopathologically, 7 cases (35%) were grade I, 10 cases (50%) were grade II and 3 cases (15%) were grade III. Regarding surgical margin, 9 cases (64.3%) had free surgical margin and 5 cases (35.7%) had involved surgical margin. Control subjects were 12 (60%) males and 8 (40%) females with a M : F ratio 3:2. Their ages ranged from 38 to 78 years with 60.35±11.13 as a mean ± SD value.
HIF-1α was expressed in overlying epidermis in 18(90%) of examined sections with cytoplasmic pattern in 6 sections(33.3%) and nucleo-cytoplasmic pattern in 12 sections (66.7%) in all layers.
HIF-1α was expressed in overlying epidermis in 95% BCC, 100% carcinoma in situ and 80%SCC cases. It was expressed in tumor masses in 35% of BCC cases and in all examined cases of in situ and invasive SCC.
Positive BCC cases had nucleo-cytoplamic pattern in 17 cases (89.5) and 2 cases (10.5) in the overlying epidermis while in tumor islands had nucleo-cytoplamic pattern. Central basaloid immunereactivity was positive in 6 cases (85.7%). Peripheral basaloid immunereactivity was positive in one case (14.3%).
from this work we can conclude that, HIF-1α may play a role in NMSC pathogensis through its effect on tumor cell survival, proliferation, invasion and metastatic spread. Also, it has an effect on cellular adaptation to hypoxia, activation of anaerobic metabolism and induction of angiogenesis. HIF-1α upregulation in NMSC cases,observed in the present study may be a compensatory mechanism to accommodate for increased proliferation and tumor hypoxia. We recommend further large scaled studies to validate and underscore current findings. Further investigation of the role of other HIFs in NMSC pathogensis and the role of HIF-1α in other cutaneous tumors.