P16和PCNA在乳房外Paget病的检测及相关性分析

目的 探讨P16和PCNA在乳房外Paget病中的表达特点及二者的关系.方法 应用免疫组化二步法检测34例乳房外Paget病及20例正常对照皮肤组织中P16和PCNA的表达.结果 乳房外Paget病组织中P16阳性率为29.4%,正常皮肤组织未见表达,两者差异有显著性(P<0.05).PCNA在乳房外Paget病组织中阳性率为85.29%,在正常皮肤组织为55.00%,两者差异有显著性(P<0.05).有淋巴结转移组中P16,PCNA的阳性表达均高于无淋巴结转移组,但P16的表达差异无显著性(P＞0.05).结论 P16和PCNA可能参与了乳房外Paget病的发病过程,并且PCNA与乳房外Paget病的淋巴结转移有关.     

乳房外Paget病皮损中P27和细胞周期蛋白E表达

目的探讨P27和细胞周期蛋白E在乳房外Paget病中的表达特点及其意义。方法应用免疫组化二步法分别检测30例乳房外Paget病患者皮损及20例正常对照皮肤中P27和细胞周期蛋白E的表达情况。结果 P27在乳房外Paget病组织中表达低于正常皮肤组织(χ~2=7.031,P0.05);细胞周期蛋白E在乳房外Paget病组织中表达高于正常皮肤组织(χ~2=27.648,P0.05)。P27和细胞周期蛋白E呈负相关关系(r=-0.437,P0.05)。P27的表达与淋巴结转移无关(χ~2=0.621,P0.05),细胞周期蛋白E的表达与淋巴结转移有关(χ~2=6.102,P0.05)。结论 P27的低表达和细胞周期蛋白E的过表达在乳房外Paget病的发生发展中可能起着十分重要的作用,并且细胞周期蛋白E与乳房外Paget病的淋巴结转移有关。     

Integrinβ1和CD44v6蛋白在皮肤黑素瘤中的表达

目的 探讨Integrinβ1和CD44v6在皮肤黑素瘤组织中的表达及意义.方法 采用免疫组化ABC法检测Integrinβ1和CD44v6蛋白在36例皮肤黑素瘤、34例色素痣及31例正常皮肤组织中的表达.结果 Integrinβ1在正常对照、色素痣和黑素瘤组织中表达的阳性率分别为41.9%,47.1%和77.7%,在黑素瘤组织中的表达强度显著高于色素痣和正常对照( P<0.05) ;CD44v6在正常对照、色素痣和黑素瘤组织中的阳性率分别为51.6%,58.8%和75.0%,三组间表达无显著差异(P＞0.05).Integrinβ1和CD44v6在黑素瘤IV～V级组和有淋巴结转移组中的表达强度显著高于I～III级组和无淋巴结转移组 (P<0.05);二者在黑素瘤组织中表达呈正相关(r=0.463,P<0.05).结论 Integrinβ1和CD44v6的表达与皮肤黑素瘤的发生发展及浸润转移有关.     

Gsk-3β、CD82和Axin1在乳房和乳房外Paget病中的表达

目的：检测Gsk-3β、CD82和Axin1在乳房和乳房外Paget病中的表达。方法：采用免疫组织化学方法检测20例乳房Paget病、20例乳房外Paget病及10例正常皮肤组织中Gsk-3β、CD82和Axin1的表达情况。结果：Gsk-3β在乳房Paget病、乳房外Paget病中的表达水平分别为(3.39±1.41)和(2.93±1.37),显著低于正常皮肤组织的(6.50±2.16),CD82表达水平分别为(6.05±2.14)和(3.90±1.75),显著低于正常皮肤组织的(10.68±1.11),Axin1表达水平分别为(2.39±1.49)和(2.77±1.64), 显著低于正常皮肤组织的(5.57±1.72)。Gsk-3β、CD82和Axin1在乳房和乳房外Paget病组织中的表达差异无统计学意义(P>0.05)。结论：Gsk-3β、CD82和Axin1在乳房和乳房外Paget病中低表达,可能与乳房和乳房外Paget病的发病有关。     

原发性乳房外Paget病中E钙黏蛋白的检测

目的观察乳房外Paget病中E钙黏蛋白的表达并分析其在肿瘤侵袭过程中的意义。方法应用免疫组化方法分别对28例原发性原位乳房外Paget病(A组)和17例原发性侵袭性乳房外Paget病(B组)标本中的E钙黏蛋白进行检测。结果原发性原位乳房外Paget病标本中E钙黏蛋白的表达较周边正常皮肤标本中表达下调,其中28例原发性原位乳房外Paget病标本中,E钙黏蛋白阴性表达的占28.6%(8/28),低表达的占46.4%(13/28),高表达的占25.0%(7/28),17例原发性侵袭性乳房外Paget病标本表达分别为17.6%(3/17),58.8%(10/17),23.6%(4/17),9例肿瘤边缘正常皮肤和2例正常阴囊皮肤中E钙黏蛋白全部高表达,正常皮肤组与两组乳房外Paget病中E钙黏蛋白的表达差异有显著性(P<0.01),而两组乳房外Paget病之间的表达差异无显著性(P>0.05)。结论E钙黏蛋白表达的下调与原发性乳房外Paget病的发病有关,但可能与侵袭过程没有必然的联系。     

PTEN和Ki67在乳房外Paget病中的表达

目的观察PTEN和Ki67在乳房外Paget病中的表达特点及其临床意义。方法应用免疫组化二步法分别检测30例乳房外Paget病患者及20例正常人皮肤组织中PTEN和Ki67的表达情况。结果PTEN在乳房外Paget病中阳性表达为66.67%,显著低于正常皮肤组织的阳性表达(100.00%,P0.05)。Ki67在乳房外Paget病中阳性表达为83.33%,显著高于正常皮肤组织中的阳性表达(50.00%,P0.05)。乳房外Paget病中PTEN表达和Ki67表达呈负相关关系(P0.05)。结论PTEN的低表达和Ki67的过表达在乳房外Paget病的发生和发展中可能起着十分重要的作用。     

CyclinA和CyclinB1在乳房外Paget病中的表达及意义

目的探讨乳房外Paget病中Cyclin A和Cyclin B1的表达及意义。方法采用免疫组化二步法检测28例乳房外Paget病及18例正常对照皮肤组织中Cyclin A和Cyclin B1的表达情况。结果 Cyclin A和Cyclin B1在乳房外Paget病组织中阳性表达率明显高于正常皮肤组。Cyclin A的表达和Cyclin B1的表达呈正相关(P0.05)。结论Cyclin A和Cyclin B1在乳房外Paget病中高表达,提示两者可能参与了乳房外Paget病的发病过程。     

外阴白色病变、鳞状上皮内瘤样变及外阴鳞状细胞癌中CD44v6的表达

目的　探讨CD44v6与外阴鳞状细胞癌发生、发展和侵袭转移的关系。方法　采用免疫组化SP法对外阴正常皮肤、外阴白色病变、鳞状上皮内瘤样变及外阴鳞状细胞癌中CD44v6进行检测。结果　正常皮肤无CD44v6表达 ;在外阴白色病变中其阳性率为 2 6.7%;鳞状上皮内瘤样变中为 5 3 .3 %;外阴鳞状细胞癌中为 73 .3 %。在外阴鳞状细胞癌中CD44v6阳性率与临床分期呈正相关 ;有淋巴结转移者阳性率为 92 .3 %,明显高于无淋巴结转移者 (P <0 .0 5 )。结论　CD44v6与外阴鳞状细胞癌淋巴结转移密切相关。     

CK5/6和CK14在乳房外Paget病的分布

目的观察细胞角蛋白5/6(CK5/6)及14(CK14)在乳房外Paget病中的表达特点,并探讨其生物学意义。方法应用免疫组化二步法分别检测34例乳房外Paget病患者皮损及20例正常对照皮肤中CK5/6及CK14的表达情况。结果 CK5/6和CK14在乳房外Paget病中阳性表达,两者主要在表皮全层弥漫性表达,表达率分别为91.17%和88.24%。结论 CK5/6和CK14在乳房外Paget病的组织来源方面起到一定的启示作用,推测乳房外Paget病的肿瘤细胞可能来源于异常分化的基底细胞层表皮干细胞。     

Pin1在乳房外Paget病的表达及意义

目的：分析Pin1染色后乳房外Paget病组和对照组切片中Pin1的表达及意义。方法：采用免疫组化染色的方法,对27例乳房外Paget病和10例正常皮肤标本进行Pin1免疫组化染色,并将乳房外Paget病组按照浸润深度分成三组分别观察。结果：乳房外Paget病组阳性率74．07％,其中51．85％为高表达,对照组阳性率30％,均为低表达,差异具有统计学意义（P〈0．05）。乳房外Paget病标本按照浸润深度分成三组进行比较,差异来自对照组与乳房外Paget病各组之间,在乳房外Paget病组内部进行两两比较无统计学意义。结论：Pin1在正常皮肤组织中不表达或极低表达,在乳房外Paget病患者皮损中的表达增高。     

CD44v6和PCNA在皮肤鳞状细胞癌中的表达及其临床意义

目的 :　研究CD4 4v6和PCNA与皮肤鳞状细胞癌 (SCC)临床病理特征的关系。方法 :　免疫组化法研究 4 8例SCC原发灶、11例淋巴结转移灶和 10例正常皮肤组织中CD4 4v6和PCNA的蛋白表达。结果 :　SCC标本中 ,CD4 4v6表达下调 (P <0 .0 1) ,分化越差下调越明显 (P <0 .0 5 ) ;PCNA表达增高 (P <0 .0 5 ) ,分化越差增高越明显 (P <0 .0 1)。二者与临床分期、淋巴结转移及发病部位均无关 (P >0 .0 5 ) ,且CD4 4v6和PCNA的表达无相关性 (r=- 0 .176 ,P >0 .0 5 )。结论 :　CD4 4v6和PCNA均可作为研究SCC发生与发展的独立的生物学指标     

CD44 and melanocytic tumors: a possible role for standard CD44 in the epidermotropic spread of melanoma

CD44 is a polymorphic family of cell membrane glycoproteins that mediate cell-matrix and cell-cell interactions involved in the mechanisms of tumor invasion and metastasis, and are subject to differential regulation during normal and malignant cell growth. We have investigated immunohistochemically the expression of CD44S and the variant isoforms CD44v3 and CD44v6 in paraffin-embedded tissue from 5 Spitz nevi, 3 compound melanocytic nevi, 2 blue nevi, 6 primary melanomas, 15 cutaneous metastases (three epidermotropic, nine dermal and three ulcerated) and 10 lymph node metastases of melanoma. Melanocytes were extensively positive for CD44S in primary melanomas and benign melanocytic proliferations. Among 15 cases of cutaneous metastases of melanoma, the three epidermotropic metastases, as well as one of the three ulcerated ones were positive for CD44S. CD44S expression was diminished or totally absent in six of the nine dermal metastases, in two of the ulcerated metastases and in seven of the ten lymph node metastases. CD44v3 and CD44v6 melanocytic expression was absent in all the lesions studied.
According to our results, selective retention of CD44S expression by melanocytes in epidermotropic metastases of melanoma seems to indicate that preservation of CD44S may contribute to the intraepidermal spread of melanoma.     

皮肤鳞状细胞癌CD44v6蛋白表达

采用免疫组织化学及图像分析技术对66例皮肤鳞状细胞癌、12例淋巴结转移灶、11例假性上皮瘤样增生、10例正常皮肤进行检测，探讨CD44v6与皮肤鳞状细胞癌的发生、发展与转移的关系。结果表明鳞状细胞癌CD44v6表达下调，且分化越差下调越明显，与是否转移及发病部位无关。提示CD44v6对维持表皮正常结构起重要作用，并与细胞增殖分化程度 有关，可以作为一个研究皮肤鳞状细胞癌发生发展的分子标志。     

Outcomes of lymph node dissection in the treatment of extramammary Paget’s disease: A single-institution study

Extramammary Paget’s disease (EMPD) often invades the dermis and metastasizes to the lymph nodes. Patients with EMPD associated with lymph node metastases have poor prognosis; to date, effective treatment has not yet been established. Lymph node dissection, aiming to control the local disease, is a standard form of management for EMPD patients with lymph node metastases (LNM). We investigated the clinical and pathological features, treatment strategies and prognostic factors of patients with metastatic EMPD who underwent lymph node dissection. We retrospectively evaluated 38 cases of extramammary Paget’s disease with lymph node metastasis over 10 years. All patients underwent wide resection of the primary lesion and lymph node dissection. Univariate analysis revealed the number of metastatic nodes and lymphadenopathy as prognostic factors. In multivariate analysis, the number of metastatic lymph nodes retained statistical significance (hazard ratio, 35.3; 95% confidence interval, 3.23–387.0; P = 0.003). The 5-year survival rate was 100% and 19.1% in patients with two or less LNM and with three or more LNM, respectively. In patients with three or more LNM, the 5-year survival rate after adjuvant radiation therapy was better than that after surgery alone (75% vs 0%). In conclusion, patients with two or less LNM can be expected to have long-term survival with lymph node dissection only, while patients with three or more LNM may require adjuvant radiation therapy to improve prognosis. These results suggest that lymph node dissection may be a strategy to treat EMPD with regional LNM.     

Evaluation of positron emission tomography imaging to detect lymph node metastases in patients with extramammary Paget's disease

Patients with extramammary Paget's disease (EMPD) have a relatively good prognosis, when spread of the tumor cells is limited to the epidermis. However, invasive EMPD has a poor prognosis, when the patients have regional lymph node metastasis. Detection of nodal metastasis is thus mandatory to manage EMPD. To evaluate the ¹⁸F‐fluorodeoxyglucose positron emission tomography (FDG‐PET) imaging to assess lymph node metastasis, 15 patients with histologically proven primary EMPD were enrolled in this study. All patients underwent whole‐body PET prior to sentinel lymph node biopsy (SLNB). The maximum standardized uptake value (SUVmax) of more than 2.5 was evaluated as positive PET indicative of malignancy. Among 14 cases with the primary genital lesions, 11 cases underwent bilateral SLNB of the inguinal nodal basin and the remaining three cases unilateral SLNB. One case with a primary axillary lesion underwent unilateral SLNB of the axillary nodal basin. Therefore, a total of 26 regional basins were investigated. In general, nodal basins can be categorized into four groups: (i) histologically negative and PET negative (true negative); (ii) histologically positive and PET negative (false negative); (iii) histologically positive and PET positive (true positive); and (iv) histologically negative and PET positive (false positive) groups. In the 26 nodal basins, there were 19 true negative and seven true positive cases, and neither false negative nor false positive cases were observed. The mean SUVmax was significantly higher in the true positive basins (8.03 ± 3.34) than in the true negative basins (0.26 ± 0.56). The SUVmax value may be useful for detection of nodal metastasis.     

CD44v6 is a marker for systemic spread in cutaneous T-cell lymphomas

Adhesion molecules are involved in leukocyte recruitment, lymphocyte recirculation, and in several aspects of tumour biology. Recent discoveries of surface proteins on tumour cells involved in tumour metastasis may explain the invasive behaviour, the migration involving reversible adhesive contacts, the release into the circulation and the extravasation of tumour cells.
CD44 is a family of glycoproteins involved in cell-cell and cell-matrix interactions. The v6 (variant exon v6) form of CD44 confers a metastatic potential onto some carcinoma cells. In the present study, the expression of CD44v6 on skin biopsies of 10 inflammatory skin diseases, 30 cutaneous lymphomas (CL), 11 reactive lymph nodes, 10 primary nodal non-Hodgkin's lymphomas (NHL) and 5 secondary nodal NHL was investigated immunohistochemically.
None of the 10 nodal NHL were CD44v6 positive for the neo-plastic B- or T-cells, whereas 11/12 CL with systemic spread showed a distinct CD44vG expression in the skin. CD44v6 was not expressed on the tumour cells of skin biopsies of patients without systemic spread (18 cases of CL). In conclusion, CD44v6 expression is connected to an aggressive behaviour of CL.     

CD44 expression in melanocytic lesions: a marker of malignant progression?

CD44 is the major human cell surface receptor for hyaluronate and functions in a diverse range of physiological processes. Alternative splicing of a single gene generates a lamily of splice variants (CD44v1-10) in addition to the standard isoform. CD44H. Expression of CD44. particularly CD44v6. has heen descrihcd to correlate with metastasis formation in various tumours, although evidence in malignant melanoma is inconclusive. In this study, we explored the immunohisto-chemical pattern of CD44 expression in a range of melanocytic lesions using a panel of monoclonal antibodies raised to CD44H and the variants v 3, v4/5. v6and v8/9. Skin biopsies of 106 lesions from 100 patients were assessed and included benign and dysplastic naevi. melanoma in situ, malignant melanomas in horizontal and vertical growth phase, and cutaneous and lymph node metastases. CD44H was highly expressed in benign and dysplastic naevi and in melanoma in situ. However, expression within melanomas diminished with increasing invasiveness. and the pattern of expres-sion observed correlated significantly with the growth phase of the lesion rather than its Brcslow thickness. CD44 splice variants were not detected in any lesions. These results suggest a possible role for downregulation of CD44H in modulating the biological behaviour of malignant melanoma.