الفهرس 
? Chapter (1( 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 metastasizes. Following local invasion and tissue destruction, SCC commonly metastasizes to lymph nodes. GLUT-1 is one of the most important glucose transporters that facilitates the transport of glucose across the plasma membranes of mammalian cells. Previous studies indicated that up regulation of GLUT-1 contributed to improve glucose metabolism which was connected with rapid proliferation of different tumors. This work aimed to investigate GLUT1expression 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 a retrospective,prospective 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 were selected from Dermatology Outpatient Clinic, Menoufia 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, Menoufia University Hospital and Tanta Cancer Center 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 GLUT- 1 antigen by using Rabbit polyclonal antibody. BCC cases were 6 (30%)males and 14 (70%) females with a M: F ratio of 3:7.Their ages ranged from 50 to 87 years with 62.15±9.60 as a mean± SD value. Lesion size ranged from 3 to 4 cm with 2.70± 0.82 as a mean ± SD value. Regardenig the site,18 cases were on the face (90%) and 2 were on the scalp (10%). Regarding the clinical subtypes of BCC, 19 cases (95%) were presented with ulcer and one case (5.0%) was presented with nodular lesion. Histopathologically18 cases (90%) had solid BCC, one case (5.0%) had adenoid BCC and one case (5.0%) had keratotic BCC . Eight cases (46.7%) had free surgical margin and 7 cases (53.3 %) had involved surgical margin. SCC in situ 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 one case(25%) was on the face. Lesion size ranged from 0.2 to1cm.Regarding the clinical presentation, 3(75%) were presented with polyps and one(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 8cm 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. GLUT1 was expressed in overlying epidermis in all examined sections with cytoplasmic pattern in 4 sections(20%) and membranocytoplasmic pattern in 16 sections (80%).In dermis Positive adnexal immunoreactivity was noted in18 cases. GLUT1 was expressed in overlying epidermis in 100% BCC,75% carcinoma in situ and 100%SCC cases. It was expressed in tumor masses in 70%,75% and 100% of BCC, carcinoma in situ and SCC cases respectively. 16 cases of BCC(88.9%) had membranous pattern and 2 cases(11.1%) had Membrano- cytoplasmic pattern in the overlying epidermis. 6 cases of BCC had membranous pattern(42.9%) and 8 cases(57.1%) had Membranocytoplasmic in tumor islands. Central basaloid immunereactivity was positive in 12 cases (85.7%). Peripheral basaloid immunereactivity was positive in one case (1.7%) and both peripheral and central basaloid immunoreactivity was positive in one case (1.7%).Two cases of carcinoma in situ had membranous pattern and one case had membrano-cytoplasmic pattern in the overlying epidermis. 12 cases of SCC (80%) had membranous pattern and 3 cases (20%) had membrano-cytoplasmic pattern in the overlying epidermis. 17 cases of SCC (85%) had membranous pattern and 3 cases(15%) had Membrano – cytoplasmic in tumor islands. Peripheral immunoreactivity was positive in 17 cases (85%) and both central and peripheral immunoreactivity was positive in 3 cases (15%). Stromal positivity was detected in all cases of BCC, carcinoma in situ and SCC respectively. Comparing overlying epidermis of BCC and SCC cases regarding GLUT1showed that, there was no statistically significant difference in any of the studied parameters. In tumor islands,GLUT1 expression (P= 0.02), expression percentage (P<0.001) and higher H score (P<0.001) were significantly associated with SCC cases. Comparing BCC cases vs Normal Skin, in overlying epidermis showed that, GLUT1 expression percentage (P<0.001) was downregulated in BCC cases compared to normal skin .Normal skin showed more diffuse GLUT1expression (P=0.004). Membranous pattern was significantly associated with BCC cases. Comparing tumor islands versus normal epidermis showed that GLUT1 expression (P=0.02) and expression percentage (P<0.001)were significantly higher in normal epidermis. Comparing NMSC cases vs Normal Skin, in overlying epidermis showed that expression percentage (P<0.001) was downregulated in NMSC cases compared to normal skin .In tumor islands of NMSC, expression percentage (P=0.004) was downregulated in NMSC cases compared to normal skin. No significant association was found between H score values and clinicopathologicl parameters in BCC. Higher H score value in tumor islands of SCC was significantly associated with nodular type (P=0.03). No significant association was found between percent of GLUT1 postivity and clinicopathological parameters in BCC cases whether in overlying epidermis or tumor islands. Higher postivity in SCC was significantly associated with nodular type (P = 0.002) and peripheral sites of lesions(P = 0.03). from this work we can conclude that GLUT1 may play a role in NMSC pathogensis through its effect on cell proliferation. The GLUT1downregulation in NMSC cases, observed in the present study may be a compensatory mechanism to accommodate for increased proliferation and energy consumption. Further large scaled studies are needed to validate and underscore current findings. Further investigation of the role of other GLUTS in NMSC pathogensis and the role of GLUT1in other cutaneous tumours are recommended.