Potential utility of uroplakin III,thrombomodulin, high molecular weight cytokeratin,and cytokeratin 20 in noninvasive,invasive, and metastatic urothelial (transitional cell) carcinomas

The morphology of urothelial carcinomas, particularly when poorly differentiated or in metastatic sites, is not distinctive and overlaps significantly with other poorly differentiated nonurothelial carcinomas. Currently, there is no widely used single marker or panel of markers to confirm urothelial origin. We evaluated a panel consisting of antibodies to uroplakin III (UROIII), thrombomodulin (THR), high molecular weight cytokeratin (HMWCK), and cytokeratin 20 (CK20) in a wide range of urothelial tumors. Immunohistochemistry was performed on 112 paraffin-embedded urothelial neoplasms: 14 low malignant potential, 16 low-grade noninvasive, 16 high-grade noninvasive, 36 invasive, and 25 metastatic and 5 small cell carcinomas of the urinary bladder. Tissue microarray analysis was used to examine 498 tissue cores of nonurothelial tumors and normal tissue using antibodies to UROIII, THR, and HMWCK. Overall positive staining results in all urothelial tumors are as follows: UROIII, 64 of 112 (57.1%); THR, 77 of 112 (68.8%); HMWCK, 88 of 110 (80%); and CK20, 53 of 110 (48.2%). The expression of the four markers varied with tumor grade and stage. All small cell carcinomas were negative for all markers. Variant morphologic subtypes showed similar staining as conventional urothelial carcinomas. Tissue microarray analysis showed no UROIII immunoreactivity in tissue cores of nonurothelial tumors. THR was expressed by a limited number of nonurothelial cores (10 of 37 [27%] non-small cell lung carcinomas, 2 of 36 [5.6%] lymphomas). HMWCK was expressed by 43.8% of non-small cell lung carcinomas and essentially absent in other nonurothelial tumor cores. Based on the results of the study, the expression of UROIII in a tumor is essentially diagnostic of urothelial origin; however, it is expressed in only slightly more than half of urothelial tumors. The coexpression of THR, HMWCK, and CK20 strongly suggests urothelial origin. The coexpression of two of three non-UROIII markers (THR, HMWCK, CK20) suggests urothelial origin but requires clinicopathologic correlation. The results of the study indicate a role for an antibody panel that includes UROIII, THR, HMWCK, and CK20 in the diagnosis of urothelial tumors.     

Sinonasal undifferentiated carcinoma,nasopharyngeal-type undifferentiated carcinoma,and keratinizing and nonkeratinizing squamous cell carcinoma express different cytokeratin patterns

Sinonasal undifferentiated carcinoma (SNUC) is a highly aggressive malignant neoplasm that is often difficult to distinguish from other poorly differentiated carcinomas arising in the sinonasal tract. To search for a differential cytokeratin (CK) expression that could be useful for diagnostic purposes, we compared the expression of a large panel of CKs in a series of 6 SNUCs, 10 poorly differentiated squamous cell carcinomas (SCCs), 10 nonkeratinizing squamous cell carcinomas (NKSCCs), and 5 nasopharyngeal-type undifferentiated carcinomas (NPTCs). SCC, NKSCC, and NPTC frequently showed immunoreactivity for CK5/CK6, CK8, CK13, and CK19. In addition, SCC and NKSCC expressed CK14, which was not detected in NPTC, and SCC expressed CK7 (60% of cases) and CK4 (30% of cases), which were absent in NKSCC and NPTC. Three NKSCCs were associated with a Schneiderian papilloma, and the results of the immunostaining were similar in the two components, with the exception of CK4 and CK7, which were expressed by the papilloma and not by the carcinoma. In contrast to other carcinomas, SNUC was characterized by the exclusive expression of CKs of simple epithelia, such as CK8 (100% of cases), CK7 (50% of cases), and CK19 (50% of cases). Thus, there are significant differences in the pattern of CK expression between SNUC, SCC, NKSCC, and NPTC, which could be of diagnostic aid. Moreover, these findings support the hypothesis that SNUC is a separate entity from SCC and NPTC of the sinonasal tract.     

A clinical investigation on renal pelvic and ureteral tumors]

Sixty-six patients with renal pelvic and ureteral tumors were treated in our hospital between June 1974 and June 1991. These cases consisted of 27 renal pelvic tumors, 31 ureteral tumors and 8 renal pelvic and ureteral tumors. Their ages ranged from 43 to 86 years old (average: 65). There were 46 males and 20 females. The surgical method involved total nephroureterectomy with a cuff for 44 patients, nephroureterectomy for 3, nephrectomy for 9, total nephroureterectomy with total cystectomy for 5 and partial ureterectomy for 2. Histologically, there were 60 transitional cell carcinomas (TCC), 2 squamous cell carcinomas (SCC) and 4 TCC with SCC. As for the pathological stage, 13 were pTa, 16 pT1, 12 pT2, 11 pT3, 13 pT4 and 1 pTX. Subsequent bladder tumors were found in 13 patients (19.7%). The overall survival rate at 1, 3 and 5 years were 80%, 68% and 52%, respectively according to the Kaplan-Meier's method. In this series, the pathological staging was the most important prognostic factor.     

CK20及Cjun在膀胱肿瘤的表达和临床意义

目的:探讨CK20及Cjun在膀胱癌中的表达和临床意义。方法:应用免疫组化SABC法检测52 例膀胱癌组织及10例正常人膀胱组织中的CK20 及Cjun 的表达。结果:52 例膀胱癌组织中48 例(92.3%)CK20阳性表达,47例(90.38%)Cjun阳性表达, 正常对照组织分别为1例(10.0%)和0例,正常对照组织与膀胱肿瘤间CK20和Cjun表达差异有统计学意义(分别为P<0.01、P<0.01);但是CK20及Cjun的表达与肿瘤分期分级及预后无明显相关。结论:CK20及Cjun在肿瘤组织中表达明显增高,但与分期分级无关。     

Overexpression of cyclooxygenase-2 in high-grade human transitional cell carcinoma of the upper urinary tract

OBJECTIVE: To examine cyclooxygenase (COX)-2 expression (a key enzyme in the synthesis of prostaglandins, and involved in carcinogenesis of human epithelial tumours) in human transitional cell carcinomas (TCCs) of the renal pelvis and ureter, and to determine whether COX-2 expression correlates with the clinicopathological characteristics of the disease. MATERIALS AND METHODS: Specimens from 144 patients with TCC of the upper urinary tract who had undergone nephroureterectomy were analysed immunohistochemically, and 23 were also analysed by immunoblotting. RESULTS: Immunoblot analysis showed COX-2 immunoreactivity in 17 (74%) of 23 tumours, but not in normal transitional epithelium. COX-2 was localized to the cytoplasm of cancer cells and expressed in 108 (75%) of 144 tumours, as assessed by immunohistochemical analysis. COX-2 expression correlated with tumour grade (P < 0.008), being detected in one of nine grade 1, 77 (79%) of 97 grade 2 and 30 (79%) of 38 grade 3 tumours. Other variables including tumour stage were not associated with COX-2 expression. CONCLUSIONS: We show for the first time that COX-2 is frequently expressed in TCC of the upper urinary tract and is associated with the degree of tumour cell differentiation, indicating that COX-2 may be involved in TCC carcinogenesis at an early and/or late stage, and could be a useful target for chemoprevention of this type of cancer.     

环氧化酶-2基因在膀胱移行细胞癌组织中的表达及其意义

目的　探讨环氧化酶 2 (COX 2 )基因在膀胱移行细胞癌组织中的表达及其临床意义。方法　采用免疫组织化学酶标记链霉素亲和生物素法 (LSAB)对 78例膀胱移行细胞癌组织进行COX 2基因表达的检测。结果　在膀胱癌中COX 2主要呈胞核表达 ,染色阳性率为 5 6.41% ;COX 2表达与膀胱移行细胞癌组织分级、分期和预后呈高度正相关 (P <0 .0 1)。结论　膀胱移行细胞癌中COX 2异常表达与肿瘤分级、分期和疾病进展等生物学行为密切相关。     

Correlation of cyclooxygenase-2 expression with molecular markers,pathological features and clinical outcome of transitional cell carcinoma of the bladder

PURPOSE: We investigated the relationship between cyclooxygenase-2 (COX-2) expression and molecular alterations commonly found in transitional cell carcinoma (TCC) of the bladder and determined whether COX-2 immunoreactivity is associated with cancer stage, progression and survival in patients undergoing radical cystectomy. MATERIALS AND METHODS: Immunohistochemical staining for COX-2 was done in archival tumor specimens from 80 patients who underwent radical cystectomy. Immunoreactivity was categorized as positive (reactivity in greater than 10% tumor cells) or negative. Microvessel density, E-cadherin, pRB, p16, p21, p53 and transforming growth factor (TGF)-beta1 and its receptors (types I and II) were also studied because evidence suggests a biological association between COX-2 and alteration of these molecules. RESULTS: COX-2 was over expressed in 62 patients (78%). COX-2 over expression was associated with muscle invasive pathological stage (p = 0.022), TGF-beta1 over expression (p = 0.004), decreased E-cadherin expression (p < 0.001), and altered expression of pRB (p = 0.003) and p16 (p = 0.006). At a median followup of 101 months COX-2 over expression was associated with disease progression (p = 0.038) and bladder cancer specific survival (p = 0.042). However, when adjusted for the effects of standard pathological features, only lymph node metastasis was associated with bladder cancer progression (p = 0.027) and mortality (p = 0.042). CONCLUSIONS: COX-2 is commonly expressed in patients with bladder TCC. Using the cutoff of 10% abnormal COX-2 expression is associated with the degree of invasiveness, alterations in TGF-beta1 and pRB/p16 pathways, and loss of cell adhesion. While COX-2 expression has limited prognostic value in patients with bladder TCC, it may serve as a target for therapy with selective COX-2 inhibitors.     

膀胱移行细胞癌中环氧化酶-2表达及其预后价值

目的探讨与膀胱移行细胞癌预后相关的新诊断方法。方法采用免疫组化SP法,检侧68例原发性膀胱移行细胞癌和10例正常膀胱组织标本环氧化酶-2(COX-2)的表达,结合临床资料,探讨其相互联系以及其表达与预后的关系。结果68例膀胱移行细胞癌组织中COX-2阳性表达率为63.2%(43/68),与病理分级、临床分期、血管浸润有关(P<0.05),而与淋巴结是否转移无显著性差异(P>0.05);对照组10例正常膀胱黏膜COX-2表达均为阴性;COX-2表达阳性生存超过5年者(54.1%)明显低于COX-2表达阴性者(91.3%)(P<0.05)。结论COX-2表达与膀胱移行细胞癌的恶性程度密切相关,检测COX-2表达对判断膀胱移行细胞癌预后有重要意义。     

The expression of cyclooxygenase in transitional cell carcinoma cell lines: its correlation with tumor differentiation, invasiveness and prostanoids production

OBJECTIVE: To evaluate the isozyme activities of COX-1 and COX-2 in TCC cells and correlate with cellular differentiation and tumor behavior.MATERIAL AND METHODS: Various TCC cell lines were characterized through several aspects: (1). to measure the content and the mRNA amount of COX-1 and COX-2, (2). to characterize the proteins of COX-1 and COX-2 by Western immunoblotting, (3). to measure the production of prostaglandin E2 and thromboxane B2 in culture media, and (4). to correlate these parameters with tumor differentiation and invasiveness.RESULTS: Seven out of 10 cell lines (70%) had significantly higher COX expression than normal urothelium. Tumors with lower-grade differentiation and less invasiveness had significantly higher content of COX-1 and COX-2 than those tumors with higher-grade differentiation and more invasive behavior (p<0.01). The expression of COX mRNA in TSGH8301, TCC8702 and RT4 were much higher than J82 which has minimal expression of COXs. Similarly, the COX-2 protein was much higher in TSGH8301, TCC8702 and RT4 when compared with J82. TSGH8301, TCC8702, and RT4 had high production of PGE2 and thromboxane B2 in their culture media. Increased secretions of PGE2 and thromboxane B2 were also observed in TCC8701, TCC9101, HT1376, and T24. The production of prostanoids is closely related to cytoplasmic COX expression of tumor cells.CONCLUSIONS: The expression of COX-1 and COX-2 is a common phenomenon in TCC cells and closely related to cellular differentiation and tumor invasiveness. The COX-2 inhibitors may play an important role in the control of TCC growth.     

Expression of CD44 protein in bilharzial and non-bilharzial bladder cancers

OBJECTIVES: To investigate the expression of CD44 protein in bilharzial and non-bilharzial bladder carcinomas, and to relate the results of immunohistochemistry to the established prognostic factors, as studies clearly show that altered adhesive function of tumour cells is important in the metastatic process and CD44 is assumed to be critical in the malignant progression of many human tumours. PATIENTS AND METHODS: The study included 55 patients with bladder carcinoma confirmed by cystoscopy and biopsy. Of the 33 patients with transitional cell carcinoma (TCC), 19 were bilharzial and 14 non-bilharzial, and of 22 with squamous cell carcinoma (SCC), 12 were bilharzial and 10 non-bilharzial. CD44 expression was measured by immunohistochemical analysis of paraffin-embedded tissue obtained from these patients after appropriate treatment (transurethral resection, partial or radical cystectomy). RESULTS: There was significantly less CD44 expression in invasive TCC than in normal urothelium and pre-invasive TCC (P = 0.05). The expression of CD44 was inversely related to the tumour grade and depth of invasion (P = 0.05). However, there was no such relation for SCC; there was no significant difference between CD44 expression in metaplastic squamous epithelium, pre-invasive and invasive SCC. The presence or absence of bilharzial ova had no apparent effect on the expression of CD44, with no significant difference between CD44 expression in bilharzial and non-bilharzial bladder carcinomas. CONCLUSIONS: These data confirm that there is a reduction in CD44 expression with increasing tumour grade and stage of TCC, and may provide an additional aid in predicting the progression of this tumour. There was no such relationship with SCC, and no difference between CD44 expression in bilharzial and non-bilharzial bladder carcinomas.     

Outcome of the treatment of invasive non-transitional cell carcinoma

BACKGROUND: We evaluated the treatment outcomes of non-transitional cell carcinoma (non-TCC) cases after radical cystectomy. METHODS: Radical cystectomy was performed in 259 invasive bladder cancer patients in our department and of these, 59 (22.7%) were non-TCC. Primary squamous cell carcinomas (SCC), adenocarcinomas and undifferentiated cancers (UC) were grouped as non-TCC of the bladder. Of the 59 non-TCC; 32 SCC, 20 UC, five adenocarcinoma and two sarcomatoid tumor cases were demonstrated. RESULTS: The 5-year disease-specific survival rate of TCC and non-TCC cases were 48.9 and 28.2%, respectively (P = 0.0016). The 5-year disease-specific survival rates of SCC and UC were 25.1 and 23.4%, respectively. The median survival time of SCC, UC and adenocarcinoma cases were 19, 12 and 6 months, respectively (P = 0.4579). The disease-specific survival rates of TCC and non-TCC cases at stage pT2NoMo were 79.1 and 27.2%, respectively (P = 0.0000). The median survival time of SCC, UC and adenocarcinoma cases were 19, 12 and 13.3 months, respectively, for the same stage. The survival time of TCC, SCC and UC cases at stage pT3NoMo were 23, 26 and 45 months, respectively (P = 0.2307). The median survival time at stages pT2-3N1Mo for the same groups were 18, 16 and 11 months, respectively (P = 0.0939). CONCLUSION: The study presented here demonstrates that both TCC and non-TCC cases have poor survival rates in locally advanced disease and that at the pT2NoMo stage the prognosis of non-TCC cases is poor when compared with TCC cases.     

Squamous cell carcinoma-associated antigen in uroepithelial carcinoma.

We investigated the clinical significance of squamous cell carcinoma (SCC) antigen determined by radioimmunoassay on patients with uroepithelial carcinoma. Serum SCC antigen levels and the positive rates were significantly higher in uroepithelial carcinoma having an SCC component than in normal controls, benign urologic diseases, other urogenital carcinomas, or in pure transitional cell carcinoma (TCC) of uroepithelial carcinomas. A substantial number of patients with pure TCC showed a positive serum level of SCC antigen. Immunohistochemical staining of SCC antigen on the uroepithelial carcinomas confirmed that some, not all, pure TCC, mostly grade 3, expressed SCC antigen in their cells. These results suggested a biologic characteristic of grade 3 TCC which is closely related to that of SCC. The serum levels of SCC antigen correlated well with the disease extensions in uroepithelial carcinoma containing SCC component. Changes in serum levels of SCC antigen following treatment reflected the clinical courses of patients, particularly in those with elevated pretreatment levels. The results of our study indicated that the determination of SCC antigen would be clinically useful for monitoring clinical courses of patients with uroepithelial carcinomas containing SCC component and of those with pure TCC whose pretreatment level was elevated.     

Clinical outcomes following radical cystectomy for primary nontransitional cell carcinoma of the bladder compared to transitional cell carcinoma of the bladder

PURPOSE: The effect of bladder cancer histological subtypes other than transitional cell carcinoma (nonTCC) on clinical outcomes remains uncertain. We conducted a multi-institutional retrospective study of patients with bladder cancer treated with radical cystectomy to assess the impact of nonTCC histology on bladder cancer specific outcomes. MATERIALS AND METHODS: A total of 955 consecutive patients underwent radical cystectomy with bilateral pelvic lymphadenectomy for bladder cancer at 3 academic institutions. TCC was present in the radical cystectomy specimen in 888 patients (93%). NonTCC histology was present in 67 patients (7%), including squamous cell carcinoma in 26, adenocarcinoma in 13, small cell carcinoma in 10 and other nonTCC subtypes (ie spindle cell carcinoma, carcinosarcoma and undifferentiated carcinoma) in 18. For patients alive at last followup median followup was 39 and 23 months for patients with TCC and nonTCC histologies, respectively. Bladder cancer specific progression and survival were assessed using Kaplan-Meier and multivariate Cox proportional hazards analyses. RESULTS: Bladder cancer specific progression and mortality did not differ significantly between patients with SCC and TCC histologies. Patients with nonTCC and nonSCC bladder cancer were at significantly increased risk for progression and death compared to patients with TCC or SCC (p <0.001). This association remained statistically significant in patients with organ confined disease (stage pT2 or lower) and patients with nonorgan confined disease (stage pT3 or higher) (p <0.001). In a multivariate analysis nonTCC and nonSCC histology was associated with an increased risk of bladder cancer progression and death (OR 2.272 and 2.585, respectively, p <0.001), even after adjusting for final pathological stage, lymph node status, lymphovascular invasion and neoadjuvant or adjuvant treatments. CONCLUSIONS: NonTCC and nonSCC histological subtype is an independent predictor of bladder cancer progression and mortality in patients undergoing radical cystectomy for bladder cancer. Patients with bladder TCC and SCC share similar stage specific clinical outcomes.     

Ependymomas of the central nervous system and adult extra-axial ependymomas are morphologically and immunohistochemically distinct--a comparative study with assessment of ovarian carcinomas for expression of glial fibrillary acidic protein

Extra-axial ependymomas are very rare but have been reported in the ovary, broad ligament, sacrococcygeal region, lung, and mediastinum. The histogenesis is obscure, and a thorough immunohistochemical analysis is lacking. We reviewed the morphologic and immunohistochemical features of 5 extra-axial ependymomas occurring in adults, 1 arising in an infantile sacrococcygeal teratoma, and a control group of 10 central nervous system (CNS) ependymomas in adults. All cases were evaluated for expression of epithelial membrane antigen, estrogen receptor (ER), progesterone receptor (PR), WT1, CD99, CK18, AE1:3, CAM 5.2, 34betaE12, CK7, CK20, synaptophysin, chromogranin, and glial fibrillary acidic protein (GFAP) using formalin-fixed, paraffin-embedded tissue. One hundred twelve ovarian carcinomas in 3 tissue microarrays were also studied with GFAP. The adult extra-axial cases demonstrated more architectural variability than the CNS cases. We observed that both the CNS and adult extra-axial ependymomas expressed GFAP diffusely, whereas only 9 stage III, high-grade ovarian serous papillary carcinomas stained with GFAP (2 strongly and diffusely and 7 exhibiting focally weak expression). There were significant immunophenotypic differences between adult extra-axial and CNS ependymomas, with extra-axial cases preferentially expressing 34betaE12 (60% vs. 0%), CK18 (100% vs. 20%), CAM 5.2 (60% vs. 10%), CK7 (80% vs. 10%), ER (100% vs. 10%), and PR (80% vs. 20%). Two spinal cord ependymomas expressed CK18, 1 expressed CK7, and 1 expressed CAM 5.2. CNS ependymomas more frequently expressed CD99 (100% vs. 20%). The following stains were not differentially expressed: epithelial membrane antigen (expressed in 2 of 15 cases, including both extra-axial and CNS ependymomas), synaptophysin (1/15), chromogranin (0/15), WT1 (8/15), AE1:3 (10/15), and CK20 (0/15). The ependymal elements of the sacrococcygeal tumor failed to express 34betaE12, CK18, CAM 5.2, and CK7, like most CNS ependymomas. The morphologic and immunophenotypic differences between extra-axial and CNS ependymomas suggest that they derive from distinct precursors and/or differentiate along distinct pathways. The differential diagnosis of extra-axial ependymomas is extensive, and GFAP expression in primary ovarian serous carcinomas, although rare, could theoretically contribute to diagnostic difficulties. ER and PR expression in extra-axial ependymomas may provide targets for hormonal therapy.     

Cyclooxygenase-2 is highly expressed in carcinoma in situ and T1 transitional cell carcinoma of the bladder

PURPOSE: We describe cyclooxygenase-2 (COX-2) expression patterns in patients with carcinoma in situ and/or stage T1 transitional cell carcinoma. We determined whether expression is associated with clinical outcome in these patients. MATERIALS AND METHODS: Immunostaining for COX-2 was performed on paraffin embedded bladder biopsy specimens from 2 independent groups of patients without muscle invasive carcinoma, including 39 with carcinoma in situ and 34 with stage T1 tumors. Immunoreactivity was scored as the percent of carcinoma in situ cells with cytoplasmic staining for COX-2 in the carcinoma in situ group and as the percent of stage T1 cells expressing COX-2 in the stage T1 transitional cell carcinoma group. We evaluated other molecular alterations, including E-cadherin, p21 and p53, because evidence suggests a biological association of COX-2 with alterations in these molecular markers. RESULTS: In the carcinoma in situ group 5 patients (13%) had no immunoreactivity, while 2 (5%), 5 (13%) and 27 (69%) had 10%, 20% and 30% or greater carcinoma in situ cells positive for COX-2, respectively. In the transitional cell carcinoma group 1 (3%), 4 (12%) and 29 (85%) patients had 10%, 20% and 30% or greater positive cells, respectively. COX-2 expression was not associated with any clinical or pathological parameters, or with molecular markers regardless of the cutoff used. It was also not associated with clinical outcomes in the stage T1 transitional cell carcinoma group. In the carcinoma in situ group COX-2 expression was significantly associated with disease recurrence using cutoffs of 0% and greater than 10% positive cells, and with disease progression using a greater than 20% cutoff. However, it was not associated with bladder cancer related survival. CONCLUSIONS: COX-2 is expressed in a high percent of patients with carcinoma in situ and stage T1 transitional cell carcinoma, supporting the rationale for chemoprevention studies with selective COX-2. We could not substantiate a role for COX-2 immunohistochemistry for the staging and prognosis of carcinoma in situ and/or stage T1 transitional cell carcinoma.     

Microcystic adnexal carcinoma: an immunohistochemical study including markers of proliferation and apoptosis

Microcystic adnexal carcinoma (MAC) is the prototype for a subset of locally aggressive adnexal carcinomas (LAACs). Ultraviolet radiation (UVR) and UVB signature p53 mutations are implicated in the etiology of the most common cutaneous carcinomas. However in MACs, the role of UVR and p53 mutations is unknown. In addition, controversy still exists regarding the patterns of differentiation within these tumors. The objective of this study was to determine the expression patterns of immunohistochemical markers for p53, Ki-67, c-erbB-2, and Bcl-2 in MACs, and to compare these patterns with two MAC histologic stimulants: sclerosing type basal cell carcinomas (sBCCs) and desmoplastic trichoepitheliomas (dTEs). Other objectives were to compare expression patterns of cytokeratin (CK) AE1/AE3, CK7, CD20, endothelial membrane antigen (EMA), Ber-EP4, CD34, alpha-smooth muscle actin (SMA), and S-100 protein in MACs with its histologic simulators, and to determine the usefulness of all the immunohistochemical studies in diagnosis. Immunohistochemical markers were performed on 10 MACs, 10 sBCCs, and four dTEs. They included p53, Ki-67, c-erbB-2, Bcl-2, CK AE1/AE3, CK7, CD20, EMA, Ber-EP4, CD34, S-100 protein, and alpha-SMA. MACs expressed p53 in less than 25% of the tumor cells in only two cases (20%), and both cases showed only moderately intense staining, whereas 80% of the sBCCs were positive and showed intense staining, and all dTEs were negative. In MACs, less than 5% of the tumor cells were Ki-67 positive, whereas the sBCCs showed 20% to 40% Ki-67-positive tumor cells and dTEs showed rare Ki-67-positive cells. Bcl-2 was expressed focally in MACs, diffusely in sBCCs, and in scattered cells in dTEs. All tumors were negative for c-erbB-2. CD34, CK7, EMA, Ber-EP4, S-100 protein, and alpha-SMA all showed a distinctive pattern of staining in MACs. Although MACs arise commonly in chronically sun-exposed skin, increased expression of p53 is not found frequently. Overexpression of c-erbB-2 does not appear to be a factor in the development and progression of these adnexal tumors. Bcl-2 is expressed in MACs, but not diffusely as in sBCCs. The low level of Ki-67 supports a low proliferative rate, and other immunohistochemical markers support divergent patterns of adnexal differentiation in MACs. Immunohistochemical studies may help to differentiate MAC from sBCCs and dTEs.     

皮肤鳞状细胞癌中Survivin，Caspase-3，COX-2的表达及临床意义

目的探讨皮肤鳞状细胞癌及癌旁正常皮肤中Survivin，Caspase-3和COX-2的表达及临床意义。方法采用免疫组织化学法和荧光实时定量PCR，检测41例鳞状细胞癌及10例癌旁正常皮肤组织中Survivin，Caspase-3和COX-2蛋白及mRNA表达情况。结果癌旁正常皮肤中Survivin，Caspase-3和COX-2蛋白的阳性表达率分别是0、90．00％、10．00％，鳞状细胞癌中阳性表达率分别是68．29％、29．27％、73．17％。与癌旁正常皮肤相比，鳞状细胞癌中Survivin，Caspase-3和COX-2mRNA相对表达量为11．21、0．13、9．85，差异有显著的统计学意义。经相关性分析，鳞状细胞癌中Survivin与Caspase-3蛋白表达呈负相关（X2=11．994，P=0．001，R==0．598）；Survivin和COX-2蛋白表达呈正相关（X2=14．415，P=0，R=0．652）。结论Survivin，Caspase-3和COX-2蛋白可能参与皮肤鳞状细胞癌的形成；Survivin和COX-2蛋白协同促进鳞状细胞癌的发展；增加Caspase-3和／或减少Survivin、COX-2蛋白表达的靶向治疗，有望成为阻止皮肤鳞状细胞癌形成、发展的新途径。