Expression of bcl-2, p53 and Ki-67 in arsenical skin cancers

To investigate the regulation of apoptosis and proliferation in arsenic-induced skin cancers, we examined the expression of bcl-2. p53, and Ki-67 using immunohistochemical staining. Thirty patients with Bowen's disease (BD), ten with basal cell carcinoma (BCC), eight with squamous cell carcinoma (SCC) and eleven of perilesional normal skin (PLN) of the non-sun exposure sites from endemic area were examined. The results showed that: 1) bcl-2 was expressed in all of the BCC homogeneously, in none of the SCC, and in 12/30 of the BD focally or homogeneously; 2) p53 was expressed in all of the arsenical skin cancers with a labelling index of 75±14% of BD, 50±17% of BCC. 61±15% of SCC, and also in all of the perilesional normal skin with a labelling index of 55±24%; 3) Ki-67 was expressed in all of the skin cancers with labelling index of 58±17% of BD. 12±7% of BCC, 47±21% of SCC, and in 9/11 of PLN with a labelling index of 41±24%. Expression of bcl-2 in BCC or BD is related to the phenotype of germinative basal cell. The constant expression of bcl-2 i early dysplastic cells of BD and the earliest expression of P53 in the basal cells of perilesional normal skin indicate that the initial step of arsenic-induced carcinogenesis is from the basal germinative cells. There is no mutual relationship between bcl-2, p53 or Ki-67 expression in any type of the arsenical skin cancers, but there is a positive correlation between p53 and Ki-67 expression identified in perilesional normal skin. BD had the highest labelling index of p53 and Ki-67.     

Sun exposure and skin cancer

By 1927 for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), and by 1955 for melanoma, the broad grounds for relating sun exposure to skin cancer had been established: that these are more frequent in residents of areas of high ambient solar irradiance, are more frequent in sun-sensitive people, occur mainly on sun-exposed body sites, are more frequent in people with high sun exposure, and are more frequent in people with benign sun-related skin conditions. The past 40 years have added both quantity and quality to the epidemiological evidence and, most recently, provided direct evidence that sun exposure is the cause of mutations in critical tumour suppressor genes in BCC, SCC and melanoma. Complete or more convincing answers are still needed to many questions of detail. They include whether the pattern of sun exposure is really important in, and acts independently of amount of sun exposure in, affecting the risk of melanoma and BCC; what the shape of the relationship between the amount of sun exposure and risk of BCC and melanoma is when the pattern of exposure is held constant; whether there really is a plateau in risk of BCC and melanoma beyond some level of the amount of exposure; whether this exposure-response relationship depends on cutaneous sensitivity to the sun and in what way; whether sunburn makes a specific contribution to the risk of skin cancer independent of the amount of sun exposure; whether sun exposure close to the time of diagnosis of skin cancer contributes anything to the development of the cancer; what the solar radiation action spectrum is for each kind of skin cancer; and whether sunscreens are effective in protecting against skin cancer.     

p73蛋白在正常人皮肤和表皮肿瘤中的表达

目的 探讨p73蛋白在正常人皮肤和不同表皮肿瘤皮损中的表达及意义。方法 应用免疫组化方法检测19例脂溢性角化病、16例基底细胞癌、11例Bowen病、5例鳞状细胞癌及10例正常人皮肤p73、p53、Ki67的表达。结果 在正常人表皮基底层、毛囊外毛根鞘最外层基底样细胞和皮脂腺生发细胞有p73的表达;在基底细胞癌和脂溢性角化病的基底样细胞、Bowen病中异形性明显的瘤细胞p73呈高表达,鳞状细胞癌和脂溢性角化病中的鳞状细胞呈弱阳性或不表达。脂溢性角化病、Bowen病、基底细胞癌、鳞状细胞癌之间p73蛋白表达差异有统计学意义(H=12.71,P<0.01),其中基底细胞癌的表达最强。Ki67在皮肤肿瘤之间差异也有统计学意义(H=14.12,P<0.01),但p53差异无统计学意义(H=2.058,P>0.05)。在各组样本中,p73的表达与p53、Ki67无显著相关性(P>0.05)。结论 p73蛋白可能在皮肤分化中起重要作用。     

A prospective study of the incidence of skin cancer and its risk factors in a Spanish Mediterranean population of kidney transplant recipients

BACKGROUND: Skin cancer is the most common malignancy occurring in kidney transplant recipients (KTRs). OBJECTIVES: Our purpose was to investigate, prospectively, the cumulative incidence of cancerous and precancerous skin lesions as well as their risk factors in a close follow-up population of KTRs from a Mediterranean area of Spain. PATIENTS AND METHODS: One hundred and seventy-four consecutive KTRs were examined at the moment of transplant and then at 6-month intervals. The cumulative incidence of skin cancer was computed. To analyse the role of potential risk factors (age at transplantation, cause of renal failure, duration of pretransplant dialysis, type of immunosuppressive regimen, sun-reactive skin type and history of occupational sun exposure), the Cox regression method was used. RESULTS: After a median follow-up of 72 months (range, 12-140), 39 patients (25.3%) developed 142 tumours [84 basal cell carcinoma (BCC) and 58 squamous cell carcinoma (SCC)]. The BCC/SCC ratio was 1.4 : 1. The cumulative incidence for skin cancer was 13% after 3 years of graft survival, increasing to 27.5% at 6 years and 48% at 10 years. Only age at the time of transplantation and occupational sun exposure had statistical significance as risk factors (P < 0.001). CONCLUSIONS: Our study confirms the high incidence of non-melanoma skin cancer among KTRs in a Mediterranean population with occupational sun exposure and the patient's age at the time of transplantation being the main risk factors. We believe that all organ transplant programs should provide educational information about protecting oneself from the sun as well as include follow-up visits by dermatologists in order to facilitate early diagnosis and treatment of skin cancer.     

Therapeutic ionizing radiation and the incidence of basal cell carcinoma and squamous cell carcinoma. The New Hampshire Skin Cancer Study Group

OBJECTIVE: To estimate the relative risk of developing basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) after receiving therapeutic ionizing radiation. DESIGN: Population-based case-control study. SETTING: New Hampshire. PATIENTS: A total of 592 cases of BCC and 289 cases of SCC identified through a statewide surveillance system and 536 age- and sex-matched controls selected from population lists. MAIN OUTCOME MEASURES: Histologically confirmed BCC and invasive SCC diagnosed between July 1, 1993, through June 30, 1995, among New Hampshire residents. RESULTS: Information regarding radiotherapy and other factors was obtained through personal interviews. An attempt was made to review the radiation treatment records of subjects who reported a history of radiotherapy. Overall, an increased risk of both BCC and SCC was found in relation to therapeutic ionizing radiation. Elevated risks were confined to the site of radiation exposure (BCC odds ratio, 3. 30; 95% confidence interval, 1.60-6.81; SCC odds ratio, 2.94; 95% confidence interval, 1.30-6.67) and were most pronounced for those irradiated for acne exposure. For SCC, an association with radiotherapy was observed only among those whose skin was likely to sunburn with sun exposure. CONCLUSIONS: These results largely agree with those of previous studies on the risk of BCC in relation to ionizing radiation exposure. In addition, they suggest that the risk of SCC may be increased by radiotherapy, especially in individuals prone to sunburn with sun exposure. Arch Dermatol. 2000;136:1007-1011     

A study of the solar effect on actinic keratoses by quantification of elastic fibres using an image analysis system.

It is widely accepted that elastotic changes of the skin are primarily an indicator of cumulative sun exposure of the dermis and are a characteristic finding of actinic keratoses. To date, there have been few reports that measure the amount of elastic tissue objectively and quantitatively, especially in actinic keratoses. The computerized image analysis method has proved useful recently in determining the area of elastic fibres. Using this method, we objectively quantified the elastotic tissue in actinic keratoses and evaluated the relationship between the degree of dermal elastosis, epidermal atypia and histological types of actinic keratoses. Of the 28 actinic keratoses studied, the average percentage area of the elastic fibre was 40.48 +/- 14.48 (mean +/- SD) percentile. There was a 3.65-fold increase in the amount of elastic fibre in actinic keratoses compared with that of seborrhoeic keratoses occurring on the face (p < 0.00001). In addition, the more severe the atypia, the greater the area of elastic fibres in a representative section of the dermis. In conclusion, we observed that on quantitative assessment of elastic tissue in actinic keratoses, the percentage area of the elastic fibres in a representative section of the dermis ranges from 34.86 to 46.11%. This result may provide information for use in histological diagnosis of actinic keratoses and evidence for the possible role of sunlight in the pathogenesis of actinic keratosis.     

Immunohistochemical study of cyclooxygenase-2 and p53 expression in skin tumors

Overexpression of cyclooxygenase-2 (COX-2) has been demonstrated in various cancers, including experimentally promoted tumors, gastrointestinal cancers, breast tumors and skin tumors. The mechanism that controls COX-2 expression is not yet clear. Currently, it is reported that COX-2 expression is frequently associated with mutated p53 genes. The goal of this study was to evaluate the expression patterns of COX-2 and p53 in several skin tumors and their correlation. An immunohistochemical method was used to investigate the expression of COX-2 and p53 proteins on formalin-fixed, paraffin-embedded tissue specimens of squamous cell carcinomas (SCC), basal cell carcinomas (BCC), Bowen's disease (BD), actinic keratosis (AK) and porokeratosis. The expression of COX-2 increased in 50% (5/10) of SCC, 80% (8/10) of BCC, 40% (4/10) of BD, 50% (5/10) of AK, and 20% (2/10) of porokeratosis cases. The expression of p53 increased in 90% (9/10) of SCC, 70% (7/10) of BCC, 70% (7/10) of BD, 50% (5/10) of AK, and 40% (4/10) of porokeratosis cases. COX-2 positivity rates of the p53-positive skin tumors were 56%, 100%, 57%, 80% and 25% in SCC, BCC, BD, AK and porokeratosis, respectively. However, the correlation between p53 and COX-2 expression in skin tumors was not statistically significant ( P  > 0.05). Our results indicate that skin COX-2 and p53 may play roles in skin tumors, but that there is no apparent correlation between the two markers.     

Expression of minichromosome maintenance 5 protein in proliferative and malignant skin diseases

BACKGROUND: The entire minichromosome maintenance (MCM) family (MCM2-7) play roles in the initiation and elongation of DNA replication. Many studies have demonstrated that MCM proteins may be better indicators of a wide variety of proliferative or cancer cells in malignant tissues. OBJECTIVES: To characterize the pattern and frequency of MCM5 expression in proliferative and malignant skin diseases in comparison with those of proliferating cell nuclear antigen (PCNA). METHODS: Twelve normal skin specimens, 12 specimens of psoriasis, 21 specimens of bowenoid papulosis (BP), 16 specimens of Bowen's disease (BD), 38 specimens of skin squamous cell carcinoma (SCC), and 11 specimens of basal cell carcinoma (BCC) were subjected to immunohistochemical staining for MCM5 and PCNA. Results MCM5 protein was expressed in the lower layers of epidermis in psoriasis, while MCM5 protein were present throughout the tumor cells in BP, BD, and moderately/poorly differentiated SCC. MCM5 protein was preferentially expressed in the periphery of well-differentiated SCC or bigger nests of BCC, although some small nests of BCC seemingly showed diffuse staining patterns. The percentages of MCM5-positive cells were 15.7% in normal skin, 21.8% in psoriasis, 75.9% in BP, 83.8% in BD, 63.5% in well-differentiated SCC, 77.5% in moderately differentiated SCC, 79.8% in poorly differentiated SCC, and 21.2% in BCC in average. Well-differentiated SCC showed a significantly lower percentage of positive cells than did moderately differentiated SCC or poorly differentiated SCC. MCM5 staining basically show a similar staining pattern to that of PCNA, but more cells tended to be stained with MCM5 than with PCNA. CONCLUSIONS: Our results demonstrate pattern and frequency of MCM5 expression in various skin diseases and suggest that MCM5 may be a useful marker to detect cell proliferation in skin tissue sections.     

Immunosuppressive level and other risk factors for basal cell carcinoma and squamous cell carcinoma in heart transplant recipients

OBJECTIVES: To examine risk factors for the development of squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) in a cohort of heart transplant (HT) recipients and, in particular, to evaluate the role of the cumulative doses of different immunosuppressive drugs. DESIGN: Prospective nonconcurrent study. SETTING: A dermatology clinic at a university hospital. PATIENTS: A total of 230 HT recipients 18 years or older at the time of transplantation with at least 3 years of follow-up. MAIN OUTCOME MEASURES: The risk of SCC and BCC in HT recipients and the relationship between development of SCC and BCC and cumulative doses of different immunosuppressive agents, controlling for other potential risk factors (age, sex, sunlight exposure, skin type, and presence of warts). RESULTS: The cumulative immunosuppressive drug dose 3 years after transplantation (calculated by a weighted linear combination of azathioprine, cyclosporine, and corticosteroid cumulative doses [WLC]) was independently associated with an increased risk of developing SCC but not BCC. On multivariate analysis, patients receiving a WLC higher than the 75th percentile 3 years after HT had a 4 times higher risk of SCC than recipients of a WLC lower than the 50th percentile 3 years after HT (95% confidence interval, 1.4-11.4; P =.008). Other significant risk factors for SCC development were older age at transplantation and a greater occupational sunlight exposure. The risk of developing BCC was only associated with older age at transplantation and skin type II. CONCLUSIONS: The risk of SCC but not of BCC in HT recipients was related to the level of global immunosuppression rather than to 1 specific drug. The level of immunosuppression should be kept as low as possible consistent with survival and function of the transplanted organ.     

p21 WAF1/cip1expression in non-melanoma skin tumors

Abnormal control of the cell cycle is closely linked to carcino-genesis. p21^WAF1/CIP1 protein is a universal inhibitor of Gl cyclin-dependent kinase and is induced by p53-dependent and -independent pathways. In order to elucidate the role of p21^WAF1/CIP1 in human skin carcinogenesis, protein expression in squamous cell carcinoma (SCC), basal cell carcinoma (BCC), Bowen's disease (BD), actinic keratosis (AK), keratoacanthoma (KA), seborrheic keratosis (SK), and normal skin was examined using an immunohistochemical method. In normal skin, a few positive cells were seen in some cases in the upper spinous layer of the epidermis; sebaceous glands also had positive cells. In cases of SK and KA, positive cells were found in the basal and suprabasal epidermal layers (proliferation pattern), and in cases of BD and AK, positive cells were seen mainly in the upper spinous layer (differentiation pattern). Cases of SCC had more positive cells and showed two staining patterns: proliferation, or mixed. Cases of BCC had no positive cells. p21^WAF1/CIP1 has some unidentified role in keratinocyte tumorigenesis, which may not be related directly to carcinogenesis.     

Elevated frequency of p53 genetic mutations and AgNOR values in squamous cell carcinoma

Background:  Epidermal squamous cell carcinoma (SCC) is a common malignancy in Pakistan. We hypothesize that it is characterized by higher frequency of p53 genetic mutations and increased AgNOR values compared with squamous cell papilloma (SCP) and basal cell carcinoma (BCC).
Experimental design: To test our hypothesis, 140 skin biopsies (including 20 normal skin, 20 SCP, 20 BCC and 80 SCC samples of various grades) were examined for p53 mutations using immunohistochemistry (IHC) and polymerase chain reaction (PCR). AgNOR staining was used for histological determination of AgNOR index.
Results:  Both markers were undetectable in normal skin and were low in SCP. They were upregulated in BCC and SCC. PCR experiments revealed p53 mutations in 70% and 96.25% of BCC and SCC, respectively. Higher AgNOR values were seen in SCC than in BCC (mean AgNOR count = 5.81 ± 31 and 8.36 ± 19; percentage of AgNOR was 43.5% and 53% in BCC and SCC, respectively). Finally, p53 IHC score was found to be related to the AgNOR index in the histological grading of BCC and SCC (r = +0.983, p < 0.0001).
Conclusion:  Our results suggest that a higher frequency of p53 genetic mutations and increased AgNOR values exist in SCC compared with BCC and SCP. 'Consequently, SCC patients may have poorer prognosis'.     

P16 is overexpressed in cutaneous carcinomas located on sun-exposed areas

BACKGROUND: Recently, an increased expression of P16, a cell cycle regulatory tumor suppressor protein, has been demonstrated in cervical squamous neoplasms as a marker of malignancy. In contrast, studies performed in skin carcinomas led to contradictory results. OBJECTIVES: Our first aim was to evaluate P16 expression in different types of non-melanoma skin cancers compared with normal skin and benign tumors. The second aim was to evaluate the relationship between P16 expression and the location of skin tumors (i.e. exposed versus non exposed sites). Finally, we also studied Ki67 expression in skin carcinomas and control biopsies. METHODS: Skin biopsy specimens with typical histologic features of squamous cell carcinoma (SCC; n = 30), Bowen's disease (BD; n = 17), basal cell carcinoma (BCC; n = 10), seborrheic keratosis (SK; n = 10) and normal human skin (NHS; n = 9) were obtained from 76 patients seen at our institution between 2001 and 2003. In all cases, P16 and Ki67 expression were evaluated by immunohistochemistry and image analysis. RESULTS: P16 overexpression was observed in 58% of cutaneous carcinomas (SCC: 60%; BD: 58%; BCC: 50%) versus 0% of SK or NHS (0%) (p = 0.006). Ki67 expression in over 5% of tumour cells was observed in 69% of cutaneous carcinomas (SCC: 54%; BD: 76%; BCC: 80%) versus 16% in the group including SK (30%) and NHS (0%) (p = 0.04). Overexpression of P16 was associated with a high rate of Ki67 positive tumour cells in 23/57 malignant skin tumors (40%). Both P16 was associated and Ki-67 were negative in 7/57 cases (12%). Sixty-eight percent of tumors located on sun-exposed areas versus 23% of those located on non sun-exposed areas overexpressed P16 (p = 0.02). CONCLUSION: Our study demonstrated that the expression of P16 and Ki67 is associated with skin carcinomas. No difference was observed according to histological types of carcinomas, suggesting that P16 and Ki67 expression did not correlate with the degree of proliferation and malignancy. Within cutaneous carcinoma specimens, P16 overexpression was significantly associated with the location on sun-exposed areas, suggesting a possible induction of P16 overexpression by UV radiation.     

The density of epidermal p53 clones is higher adjacent to squamous cell carcinoma in comparison with basal cell carcinoma

BACKGROUND: It is well accepted that ultraviolet radiation from the sun can induce and promote growth of skin tumours. Skin cancer develops as a consequence of multiple genetic hits, where an initial, important step includes proliferation of cells susceptible to malignant transformation. Foci of morphologically normal epidermal keratinocytes overexpressing p53 protein are common in chronically sun-exposed skin. Such foci have previously been shown to represent expanding clones of p53-mutated keratinocytes. Although several characteristics concerning epidermal p53 clones remain to be resolved, an important role in skin carcinogenesis is anticipated. The density of epidermal p53 clones in human skin is largely unknown. OBJECTIVES: To compare the occurrence of epidermal p53 clones in skin surrounding cancers with that in skin surrounding benign melanocytic naevi. To assess the influence of age on frequency and size of epidermal p53 clones in human facial skin. METHODS: We have analysed the number and sizes of epidermal p53 clones in skin specimens from patients with squamous cell carcinoma (SCC), basal cell carcinoma (BCC) and benign melanocytic naevi. Cases included normal facial skin from four different age groups. Tissue sections were immunohistochemically stained and the presence of p53 clones was recorded. Approximately 1.4 m of epidermis from a total of 112 biopsies was analysed. RESULTS: We found 128 epidermal p53 clones in biopsy specimens from 112 patients. The results showed that the number and size of p53 clones increase with age. In normal skin adjacent to SCC p53 clones were significantly more numerous and greater in size in comparison with those in normal skin both adjacent to benign naevi and adjacent to BCC. Interestingly, normal skin in the close vicinity of BCC and melanocytic naevi showed similar results regarding both number and size of epidermal p53 clones. CONCLUSIONS: Our findings suggest a connection between development of epidermal p53 clones and SCC.     

Distribution and expression of type VI collagen in photoaged skin

BACKGROUND: Several of the characteristic clinical features of photoaged skin, including wrinkling, are thought to be dependent on changes in the dermal matrix brought about by chronic sun exposure. Such changes include reductions in collagens I, III and VII, an increase in elastotic material in the reticular dermis and a marked reduction in the microfibrillar glycoprotein fibrillin. OBJECTIVES: To examine whether type VI collagen, a microfibrillar collagen necessary for cell-cell and cell-matrix communication, is affected by the photoageing process. METHODS: Six healthy volunteers with moderate to severe photoageing were enrolled into the study. Immunohistochemistry and in situ hybridization histochemistry were used to examine the levels of type VI collagen in photoprotected and photoaged sites. RESULTS: In photoprotected skin, type VI collagen was concentrated in the papillary dermis immediately below the dermal-epidermal junction, around blood vessels, hair follicles and glandular structures. The distribution of type VI collagen was unchanged in photoaged skin, although we observed an increase in the abundance of the alpha3 chain of collagen VI in the upper papillary dermis, at its junction with the dermal-epidermal junction (P < 0.05). No alterations were observed for any alpha chain at the mRNA level. CONCLUSIONS: These studies suggest that chronic sun exposure (photoageing) has little or no effect on either the distribution, abundance or levels of expression of type VI collagen in human skin. Thus, type VI collagen, unlike other matrix components so far studied, appears to be relatively unaffected by the photoageing process.     

NUAK2 localization in normal skin and its expression in a variety of skin tumors with YAP

BackgroundNUAK2 is a critical gene that participates in the carcinogenesis of various types of cancers including melanomas. However, the expression patterns of NUAK2 in normal skin and in various types of skin tumors have not been fully elucidated to date.ObjectivesTo elucidate the distribution and localization of NUAK2 expression in normal skin, and characterize the expression patterns of NUAK2 and YAP in various types of skin tumors.MethodsIn this study, we characterized the expression of NUAK2 in tissues by developing a novel NUAK2-specific monoclonal antibody and using that to determine NUAK2 expression patterns in normal skin and in 155 cases of various types of skin tumors, including extramammary Paget’s disease (EMPD), squamous cell carcinoma (SCC), Bowen’s disease (BD), actinic keratosis (AK), basal cell carcinoma (BCC) and angiosarcoma (AS). Further, we analyzed the expression patterns of YAP and p-Akt in those tumors.ResultsOur analyses revealed that NUAK2 is expressed at high frequencies in EMPD, SCC, BD, AK, BCC and AS. The expression of p-Akt was positively correlated with tumor size in EMPD (P = 0.001). Importantly, the expression of NUAK2 was significantly correlated with YAP in SCC (P = 0.012) and in BD (P = 0.009).ConclusionsOur results suggest that the YAP-NUAK2 axis has critical importance in the tumorigenesis of SCC and BD, and that therapeutic modalities targeting the YAP-NUAK2 axis may be an effective approach against skin tumors including SCC and BD.     

Solar elastosis and presence of mast cells as key features in the pathogenesis of melasma

Melasma is an acquired hypermelanosis on sun-exposed areas. Its pathogenesis has not been clearly elucidated. Using histochemistry (Giemsa, Verhoeff-van Gieson and Fontana-Masson staining), we evaluated melasma lesions and compared them with nonlesional skin. Skin samples were obtained from lesional and nonlesional facial skin of 27 patients with melasma, and biopsies were also taken from normal control subjects. Mast cells and solar elastosis areas were evaluated using a computer-assisted image-analysis program. Lesional skin had abundant elastotic material compared with nonaffected skin (13.3 +/- 2.8% vs. 10.2 +/- 2.9%, P < 0.001). Mast cells were more prominent in the elastotic areas of melasma skin (173 +/- 57% vs. 145 +/- 57%, P = 0.04). Melasma could be a result of a cumulative sun exposure, in a microenvironment of cutaneous photoageing in which inflammatory cells, particularly mast cells, play a key role.     

环氧化酶-2在表皮肿瘤中的表达

目的 探讨环氧化酶-2在不同表皮肿瘤中的表达及意义。方法 选择鳞状细胞癌8例、基底细胞上皮瘤10例、Bowen病8例和脂溢性角化病12例,运用免疫组化方法观察肿瘤细胞中环氧化酶-2的表达。结果 与正常表皮相比,环氧化酶-2在鳞状细胞癌、Bowen病、基底细胞上皮瘤中的表达明显上调,尤其以鳞状细胞癌中的表达最强。而环氧化酶-2在脂溢性角化病中的表达与正常人皮肤的表达近似。结论 环氧化酶-2表达的上调可能在表皮肿瘤的发生发展中发挥一定作用。     

组织蛋白酶D在皮肤鳞状细胞癌、基底细胞癌和脂溢性角化病的组织表达及其意义

目的：观察组织蛋白酶D（cathepsinD，CD）在皮肤鳞状细胞癌（SCC）、基底细胞癌（BCC）、脂溢性角化病（SK）的组织表达，分析其表达差异及其意义。方法：用免疫组化SP染色法检测CD在15例SCC、15例BCC、14例SK及10例正常对照皮肤组织中的表达。结果：CD在正常皮肤组织表达为阴性．在SK、BCC、SCC瘤组织中表达依次升高，在SCC、SK之间表达有显著性差异（P〈0．05）；CD在SK、BCC、SCC间质细胞表达阳性率分别为85．7％、66，7％、33．3％。结论：CD的表达水平可能与SCC侵袭和转移有关。     

Immunohistochemical prognostic criteria in xeroderma pigmentosum

Xeroderma pigmentosum (XP) is a rare inheritable disease characterized by severe sun sensitivity and early development of skin cancers. We compared the expression of cell proliferation markers and cell cycle checkpoint regulators in squamous cell carcinomas (SCC) and basal cell carcinomas (BCC) from patients with and without XP. Immunostaining for p53, Ki-67, and proliferating cell nuclear antigen (PCNA) was determined in SCCs and BCCs from 18 XP patients and 30 controls. Nine of the 18 XP patients had SCC and BCC, and the other nine had only SCC. In the control group, 15 moderately differentiated SCCs and 15 BCCs were evaluated. Expressions of p53, Ki-67 and PCNA in XP and non-XP patients were assessed statistically by using the Chi-square method. Expression of Ki-67 and PCNA was found to be greater in SCC from XP patients than controls (P = 0.021 and P = 0.033, respectively). Expression of PCNA and p53 by BCCs was greater in XP patients (P < 0.001 and P = 0.027, respectively). There was a significant difference in Ki-67 (P < 0.001) and PCNA (P = 0.001) expression between the lesions of the XP patients who died during the follow up and XP patients who survived. In XP patients, SCCs with more than 10% Ki-67 expression and %50 PCNA expression have a poor prognosis. Our results suggest that increased Ki-67 and PCNA expression may be a predictor for recurrence of nonmelanocytic skin cancer and a poor prognosis.