Diagnosis and treatment of basal cell and squamous cell carcinomas

Rates of squamous cell and basal cell carcinomas have been increasing, possibly as a result of increased exposure to ultraviolet radiation. Primary care physicians can expect to diagnose six to seven cases of basal cell carcinoma and one to two cases of squamous cell carcinoma each year. Basal cell carcinomas may be plaque-like or nodular with a waxy, translucent appearance, often with ulceration and telangiectasia. They rarely metastasize and are treated with excision, cryotherapy, electrodesiccation and cautery, imiquimod, 5-fluorouracil, or photodynamic therapy (the latter is not approved for this purpose by the U.S. Food and Drug Administration), although surgery results in the fewest recurrences. Actinic keratoses are scaly keratotic patches that often are more easily felt than seen. They are amenable to any of the destructive techniques described above, with the exception of photodynamic therapy. Squamous cell carcinomas arise from keratotic patches and become more nodular and erythematous with growth, sometimes including keratin plugs, horns, or ulceration. Because they may metastasize, they often are treated with excisional biopsy.     

Differential protease expression by cutaneous squamous and basal cell carcinomas.

To assess the postulated role of plasminogen activation in tumor invasion, we have investigated the cellular sites of synthesis for urokinase-type (uPA) and tissue-type (tPA) plasminogen activators and their inhibitors (PAI-1 and PAI-2) in two human cutaneous neoplasia that differ in their metastatic potential. The combined use of zymography on tissue sections and in situ hybridization demonstrates that uPA is produced by malignant cells of squamous cell carcinomas (SCC) but not by basal cell carcinomas (BCC), whereas tPA is detected exclusively in nonmalignant dermal tissue. In addition, we show that SCC neoplastic cells simultaneously produce variable amounts of PAI-1, and that PAI-1 production correlates inversely with uPA enzymatic activity. These observations establish that invasive human malignant cells in vivo can activate plasminogen through uPA production during the early phases of tumor growth; they also demonstrate that the proteolytic activity of tumor cells can be modulated by the concomitant production of PAI-1. Because SCC have a higher invasive and metastatic potential than BCC, our findings lend further support to the involvement of plasminogen activation in malignant behavior.     

Ornithine decarboxylase is a target for chemoprevention of basal and squamous cell carcinomas in Ptch1+/- mice

Solar ultraviolet B (UVB) radiation induces cutaneous ornithine decarboxylase (ODC), the first enzyme in the polyamine-biosynthesis pathway, which drives continued proliferation and clonal expansion of initiated (mutated) cells, leading to tumorigenesis. Therefore ODC is a potentially important target for chemoprevention of basal cell carcinomas (BCCs), the majority of which have mutations in the tumor-suppressor gene known as patched (PTCH). To assess this possibility, we first overexpressed ODC in the skin of Ptch1+/- mice using a keratin 6 (K6) promoter that directs constitutive ODC expression in the outer root sheath of the hair follicle. UVB irradiation of these mice accelerated induction of BCCs as compared with their Ptch1+/- littermates. To further verify the role of ODC in BCC tumorigenesis, we used an antizyme (AZ) approach to inhibit ODC activity in the Ptch1+/- mice. Ptch1+/- mice with AZ overexpression driven by the K6 promoter were resistant to the induction of BCCs by UVB. Furthermore, oral administration of the suicidal ODC inhibitor alpha-difluoromethylornithine reduced UVB-induced BCCs in Ptch1+/- mice. These results demonstrate the crucial importance of ODC for the induction of BCCs and indicate that chemopreventive strategies directed at inhibiting this enzyme may be useful in reducing BCCs in human populations.     

Immunoprevention of basal cell carcinomas with recombinant hedgehog-interacting protein

Basal cell carcinomas (BCCs) are driven by abnormal hedgehog signaling and highly overexpress several hedgehog target genes. We report here our use of one of these target genes, hedgehog-interacting protein (Hip1), as a tumor-associated antigen for immunoprevention of BCCs in Ptch1+/- mice treated with ionizing radiation. Hip1 mRNA is expressed in adult mouse tissues at levels considerably lower than those in BCCs. Immunization with either of two large recombinant Hip1 polypeptides was well tolerated in Ptch1+/- mice, induced B and T cell responses detectable by enzyme-linked immunosorbent assay, Western blot, delayed type hypersensitivity, and enzyme-linked immunospot assay, and reduced the number of BCCs by 42% (P < 0.001) and 32% (P < 0.01), respectively. We conclude that immunization with proteins specifically up-regulated by hedgehog signaling may hold promise as a preventive option for patients such as those with the basal cell nevus syndrome who are destined to develop large numbers of BCCs.     

p16过表达可识别HPV阳性的外阴鳞状细胞癌(英)

根据与人乳头状病毒（HPV）的关系，外阴鳞状细胞癌可分为两类：HPV相关的基底细胞样癌或疣状癌和非HPV相关的分化性角化型癌。近来提出用p16和p53的免疫组化染色来区分这两类外阴鳞癌。为评价免疫组化在外阴鳞癌分类中的作用、阐明这两类外阴鳞癌的临床病理特征，本课题对92例外阴鳞癌进行了p16、p53的免疫组化染色，并用2组不同引物PCR对HPV进行检测和分型。92例中16例检测出nPV（17．4％），其中HPV16占阳性病例的75％。组织学与HPV检测结果之间存在较大差异，阳w阳性病例的37．5％表现为角化型，而HPV阴性病例的9．2％显示基底细胞样或疣状型。p16和p53阳性表达率在HPV阳性肿瘤中分别为100％和6．2％，而在HPV阴性肿瘤中分别为2．3％和64．5％。     

Squamous cell and basal cell carcinomas: preliminary study of 3,817 primary skin cancers

A series of patients with 3,817 cutaneous carcinomas of different types observed in a private practice setting is reported. Preliminary computerized analyses indicate that 88% of these squamous cell and basal cell carcinomas were less than 25 mm. Scalpel surgery, curettage and desiccation, or radiation therapy was used for most tumors and an overall cure rate of greater than 98% was obtained. A pretreatment biopsy allowed for selection of the most appropriate management and authoritative instructions for long-term follow-up visits and prophylaxis.     

骨折髋支撑关节治疗股骨颈骨折的实验研究

摘要：目的 通过动物实验探讨一种新的非限制性支撑固定装置—骨折髋支撑关节对新鲜头下型股骨颈骨折的治疗效果。方法 采用骨龄成熟的杂交犬32只，术中造股骨颈头下型骨折并股骨头脱位的动物模型。实验组用手术植入骨折髋，坚强固定骨折端、减轻并替代股骨头负重。对照组复位后用两枚螺丝钉固定骨折端。结果24周实验组骨折线区形成规则骨小梁并出现髓细胞、股骨头轻度纤维化，对照组骨折线区仍为类骨组织，股骨头坏死并塌陷变形。48周实验组骨折线区骨小梁改建，髓细胞丰富，股骨头恢复正常。对照组骨折线区出现少量不规则骨小梁。股骨头坏死塌陷并吸收。 结论 骨折髋支撑关节能有效的治愈股骨颈骨折并能有效的防止股骨头坏死。     

Localization of integrin receptors for fibronectin, collagen, and laminin in human skin. Variable expression in basal and squamous cell carcinomas.

VLA integrins in human skin were examined by indirect immunofluorescence utilizing antibodies recognizing the beta 1, alpha 2, alpha 3, or alpha 5 subunits. Staining of fetal, newborn, or adult skin with antibodies to beta 1, alpha 2, or alpha 3 subunits gave essentially similar staining patterns: intense staining was associated with the basal layer of the epidermis, hair follicles, and blood vessel walls. The alpha 5 subunit could be detected only in epidermis and the inner root sheath of hair follicles in fetal skin. In epidermis, the staining reaction for the beta 1 subunit was not only found in sites interfacing with the basement membrane zone, but also around the entire periphery of these cells. We speculate that these receptors might have previously unrecognized functions in cell-cell interactions or that these findings may suggest the presence of previously unrecognized ligands in the intercellular spaces of keratinocytes. Examination of nine nodular basal cell carcinomas revealed a prominent staining reaction with anti-beta 1 and anti-alpha 3 antibodies at the periphery of the tumor islands. In contrast, staining of five squamous cell carcinomas revealed either the absence of integrins or altered and variable expression. Thus, matrix components and their receptors may participate in modulation of growth, development, and organization of human skin.     

肺癌EGFR的表达及意义

目的　探讨EGFR在肺癌中的表达及与癌组织分型、淋巴结转移等方面的关系。方法　应用免疫组化S P法分别对 86例肺癌组织、35例正常肺组织EGFR的表达进行检测。结果　肺癌组织EGFR的表达明显高于正常肺组织。EGFR在鳞癌与腺癌中的表达无显著差异。淋巴结转移阳性癌组织EGFR表达与淋巴结转移阴性癌组织比较 ,无明显差别。结论　EGFR参与了肺癌的发生发展。EGFR表达与鳞癌、腺癌分型无关 ,与淋巴结转移与否无关。     

Autophagy modulators for the treatment of oral and esophageal squamous cell carcinomas

Oral squamous cell carcinomas (OSCC) and esophageal squamous cell carcinomas (ESCC) exhibit a survival rate of less than 60% and 40%, respectively. Late-stage diagnosis and lack of effective treatment strategies make both OSCC and ESCC a significant health burden. Autophagy, a lysosome-dependent catabolic process, involves the degradation of intracellular components to maintain cell homeostasis. Targeting autophagy has been highlighted as a feasible therapeutic strategy with clinical utility in cancer treatment, although its associated regulatory mechanisms remain elusive. The detection of relevant biomarkers in biological fluids has been anticipated to facilitate early diagnosis and/or prognosis for these tumors. In this context, recent studies have indicated the presence of specific proteins and small RNAs, detectable in circulating plasma and serum, as biomarkers. Interestingly, the interplay between biomarkers (eg, exosomal microRNAs) and autophagic processes could be exploited in the quest for targeted and more effective therapies for OSCC and ESCC. In this review, we give an overview of the available biomarkers and innovative targeted therapeutic strategies, including the application of autophagy modulators in OSCC and ESCC. Additionally, we provide a viewpoint on the state of the art and on future therapeutic perspectives combining the early detection of relevant biomarkers with drug discovery for the treatment of OSCC and ESCC.     

p27、p53蛋白在口腔鳞癌中的表达和意义

目的 探讨口腔鳞癌中p27与p53基因表达特征和临床病理意义。方法 对38例口腔鳞癌组织采用免疫组化方法检测p27及p53蛋白表达。结果 38例口腔鳞癌中印蛋白阳性表达22例，阳性率57．9％，p53阳性表达21例，阳性率55．3％。p27在鳞癌Ⅰ级中阳性表达17例（68．0％），Ⅱ级中阳性2例（40．0％），Ⅲ-Ⅳ级中阳性3例（37．5％）。p53在鳞癌Ⅰ级病例中阳性10例（40．0％），Ⅱ级中1例（20．0％），Ⅲ，Ⅳ级中7例（87．5％）。结论 p27蛋白阳性表达率随病理恶性程度增高而降低，但无统计学意义。p53蛋白阳性表达率随病理恶性程度升高而增高，提示D53基因与口腔鳞癌细胞分化有相关性。p27和p53表达在鳞癌中呈负相关。     

miRNAs in human papilloma virus associated oral and oropharyngeal squamous cell carcinomas

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer in the world with 600,000 new cases diagnosed annually. Tobacco and alcohol use have been associated as the principal etiological factors of this pathogenesis. The incidence of smoking-associated HNSCC has declined, while human papilloma virus (HPV)-associated HNSCC is on the rise. There are currently no clinically validated biomarkers to detect this cancer at an early stage (cancers independent of HPV status). It is well-established that the aberrant expression of miRNAs can lead to tumorigenesis. miRNA expression differences have also been demonstrated in HPV-positive and HPV-negative HNSCC tumor tissues as well as in body fluids. Therefore, miRNAs have the potential to provide an unprecedented insight into the pathogenesis of HNSCC and serve as potential biomarkers. This review addresses HNSCC disease burden and the regulation of miRNA by HPV viral oncoproteins, potential miRNA biomarkers and future perspectives. miRNA provides an unique opportunity to fulfill the current clinical challenge in HNSCC patient management by enabling early detection followed by targeted interventions, leading to a significant reduction in mortality and morbidity.     

Synchronous and metachronous squamous cell carcinomas of the head,neck and esophagus

Thirty-four (1%) of 3,287 patients with squamous carcinoma of the head-neck developed carcinoma of the esophagus. The clinical and radiological importance of this relationship is emphasized. Since there is an increased incidence of esophageal carcinoma in this group, perhaps all such patients should have an annual esophagogram.     

食管鳞状细胞癌中热休克蛋白27的表达及其意义

目的:探讨食管鳞状细胞癌(食管鳞癌)中热休克蛋白27(HSP27)的表达及其意义。方法:应用免疫组化Envision二步法,观察134例食管鳞癌和22例切缘食管黏膜中HSP27的表达,并比较其阳性率。结果:食管鳞癌和切缘食管黏膜中HSP27的阳性率分别为50.0%和22.7%;食管鳞癌中HSP27阳性率明显高于切缘食管黏膜(=11.982,P<0.001)。HSP27在高、中、低分化食管鳞癌的阳性率分别为65.3%、50.8%、13.6%,表达差异有极显著意义(=13.816,P<0.001)。HSP27的阳性表达与区域淋巴结转移无关(=0.0845,P>0.05)。结论:食管鳞癌是HSP27高表达肿瘤。HSP27的表达阳性率随着食管鳞癌分化程度的降低而降低。χ2sχ2sχ2s     

牙龈鳞癌中WWOX基因的表达及其临床意义

目的：研究WWOX基因在牙龈鳞癌组织中的表达及意义。方法：应用免疫组化SP法检测70例牙龈鳞癌组织中WWOX基因的表达,并与临床病理指标结合进行分析。结果：牙龈鳞癌组织中ww0X基因的阳性率为27．14％。WWOX基因的表达与牙龈鳞癌的病理分级、淋巴结转移有相关性（P〈0．05）,与临床分期明显相关（P〈0．05）。WWOX基因在牙龈鳞癌中的表达呈负相关性。结论：WWOX基因参与牙龈鳞癌的发生发展过程,可作为评估牙龈鳞癌生物学行为的一项指标,用于识别高危转移和不良预后者及为判断其生物学特性提供可靠的指标。     

Oncolytic herpesvirus effectively treats murine squamous cell carcinoma and spreads by natural lymphatics to treat sites of lymphatic metastases

Oncolytic herpesviruses have significant antitumoral effects in animal models when delivered directly to established tumors. Lymphatic metastases are a common occurrence for many tumor types. This study investigates the potential of an attenuated, replication-competent, oncolytic herpes simplex virus (NV1023) both to treat a primary tumor by direct injection and to travel through the lymphatic system to treat metastatic tumor within the lymph nodes draining lymph from the site of primary cancer. Isosulfan blue dye was injected into murine auricles to determine normal lymphatic drainage patterns and demonstrated consistent blue staining of a group of ipsilateral cervical lymph nodes. Auricular injections of NV1023 resulted in viral transit to these lymph nodes as measured by 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside histochemistry and viral plaque assay. An oncolytic herpesvirus (NV1066) expressing green fluorescent protein also demonstrated viral transit from the auricle to the cervical lymph nodes on fluorescence microscopy. Using the SCC VII cell line, a novel murine model of auricular squamous cell carcinoma was developed with an approximately 20% incidence of cervical lymph node metastases. Delivery of NV1023 or NV1066 to the surgical beds after excision of auricular SCC VII tumors resulted in successful viral infection of metastatic SCC VII cells within the cervical lymph nodes. After a 7-week follow-up, significantly enhanced locoregional control (p < 0.05, Fisher exact test) and disease-free survival (p < 0.05, log rank test) were evident with NV1023 treatment. This study demonstrates that the delivery of an oncolytic herpesvirus to a primary tumor site after surgical excision may have a significant impact on reducing both primary site recurrence and regional nodal metastases.     

消化道外基底细胞样鳞状细胞癌4例临床病理分析

目的 对基底细胞样鳞状细胞癌(BSCC)的临床病理特点、组织起源、诊断与鉴别诊断等进行初步探讨.方法 对4例消化道外BSCC做常规石蜡切片,行HE和免疫组化染色.结果 4例中男性1例,女性3例,发病年龄分别为26、58,66和70岁.4例肿瘤分别位于右下鼻道和右上颌窦腔、腭部正中硬软腭交界处、右上臂皮肤及头顶部皮肤.结论 BSCC常呈浸润性生长,肿瘤表面多有溃疡形成,镜下瘤细胞小,呈基底细胞样,排列成实性巢状及条索状,在瘤细胞巢周围的细胞排列成栅栏状,在中央可见特征性的粉刺样坏死.2例BSCC中可见局灶性鳞状细胞分化及角化.免疫组化瘤细胞上皮及肌上皮标记阳性.BSCC须与多种其他恶性肿瘤相鉴别.