Chondroid syringoma: an immunohistochemical study using antibodies to Ca 15-3, KA-93, Ca 19-9, CD44 and BM-1

The expression of Ca 15-3, KA-93, Ca 19-9, CD44 and BM-1 in normal skin and chondroid syringoma was investigated immunohistochemically using antibodies to these antigens.
In the normal skin, the eccrine ducts and/or secretory elements were positive for all these antigens. On the other hand, the apocrine ducts and/or secretory elements were positive for the antibodies to Ca 15-3, KA-93 and CD44.
In chondroid syringoma, the luminal cells of tubnloglandular structures were positive for the antibodies to Ca 15-3 and BM-1, and partly positive for those to KA-93 and Ca 19-9. The basal cells of the tubular structures and solid nests were positive only for the antibody to CD44. Stromal cells in the myxoid area were positive for the antibodies to KA-93 and CD44, and the chondroid matrix was positive for the antibody to BM-1.
It is suggested that chondroid syringoma might originate from, or differentiate into the ducts and/or secretory elements of the eccrine sweat glands. In addition, the significance of the expression of BM-1 in the chondroid matrix is discussed.     

CD44 expression in normal and inflamed skin

CD44 is the principal cell surface receptor for hyaluronate. In non-inflamed skin, CD44 expression is limited to the cell membrane of eccrine coil cells. The distribution on these cells is assymetric, with intense staining on the dermal side and little staining on the luminal side of the coil cell. In skin containing a pathologic process, either inflammatory or neoplastic, CD44 expression can be widespread on the membranes of keratinocytes and on infiltrating lymphocytes in the vicinity of the process. Diverse roles have been proposed for CD44 and largely involve aspects of cellular adhesion in one setting or another. CD44 may identify a more mobile, proliferating keratinocyte that is responding to local injury. In eccrine coil, the stable presence of CD44 on the non-luminal surface of secretory cells indicates an undefined function for CD44 in the generation of eccrine sweat.     

乳房外佩吉特病中囊泡病液体蛋白15的表达及其意义

目的：分析乳房外佩吉特（Paget）病中囊泡病液体蛋白（GCDFP）-15的表达及其意义。方法：应用免疫组化方法对20例乳房外Paget病患者的GCDFP-15和细胞角蛋白20（CK20）进行检测。结果：20例患者CK20均为阴性,8例呈侵袭性生长的患者GCDFP-15表达为强阳性或阳性,12例呈原位生长的患者GCDFP-15表达为弱阳性或阴性。结论：GCDFP-15的表达对于判断乳房外Paget病是否呈侵袭性生长有一定意义。     

Matrilysin-1 (MMP-7) and MMP-19 are expressed by Paget's cells in extramammary Paget's disease

BACKGROUND: Extramammary Paget's disease (EMPD) is a rare malignant neoplasm of apocrine gland bearing skin characterized by intraepidermal proliferation of adenocarcinoma cells. Tumor growth depends on the ability of tumor cells to migrate by proteolysis and on angiogenesis. The matrix metalloproteinase (MMP) enzymes have been implicated in both of these processes in other types of skin cancer. METHODS: The expression of MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-13, and MMP-19 was analyzed by immuno- histochemistry and/or in situ hybridization in 27 EMPD and five mammary PD (MMPD) specimens. The distribution of laminin-5 (LN-5) and tenascin-C, two extracellular matrix proteins associated with tumor invasion, was studied by immunohistochemistry. RESULTS: MMP-7 (matrilysin-1) and MMP-19 were the most frequently expressed MMPs in Paget's cells. Overexpression of MMP-2, MMP-9, or MMP-13, which is seen in many cancers, was not evident in EMPD. LN-5 and tenascin-C positivity did not correlate with the level of invasion. MMP-7, MMP-13, and MMP-19 were detected abundantly in MMPD, while MMP-9 was absent. CONCLUSIONS: MMP expression did not generally associate with the level of invasion of EMPD. In three samples positive for MMP-7 and four samples positive for MMP-19, an underlying carcinoma was detected, suggesting the importance of these two MMPs as predictors of secondary EMPD or the putative origin of Paget's cells from the dermal adenocarcinoma cells of apocrine duct origin.     

Keratin profile of intraepidermal cells in Paget's disease,extramammary Paget's disease,and pagetoid squamous cell carcinoma in situ

BACKGROUND: Although the histopathologic differential diagnosis of pagetoid neoplasms is broad, unique histopathologic identifiers and clinical correlation can often identify the process. However, in the case of mammary Paget's disease (MPD) or extramammary Paget's disease (EPD) without an obvious underlying malignancy, distinction from pagetoid squamous cell carcinoma in situ (PSCCIS) can be challenging. Our goal was to better define the immunohistochemical staining patterns of these three entities in the hope of determining distinctive staining patterns. METHODS: We evaluated nine cases of PSCCIS, five cases of MPD, and 10 cases of EPD with the immunohistochemical antibodies CAM 5.2 and CK 5/6. In addition, only PSCCIS was stained with CK 7, as the staining patterns of CK 7 in MPD and EPD are well known from prior studies. RESULTS: CAM 5.2 diffusely stained all cases of MPD and EPD and failed to stain any case of PSCCIS. Furthermore, CK 7 only focally stained two of the 10 cases of PSCCIS. CK 5/6 was difficult to interpret due to the high functional background staining of the normal keratinocytes in the epidermis. CONCLUSIONS: Based on these results, our data supports the use of CAM 5.2 and CK 7 immunoperoxidase markers in differentiating between difficult cases of PSCCIS and MPD or EPD. An antibody panel consisting of S-100, CAM 5.2, and CK 7 will aid in the accurate diagnosis of almost all pagetoid neoplasms of the breast or genital skin.     

Replication of Paget cells in mammary and extramammary Pageťs disease

Replication of Paget cells in mammary and extramammary Paget's disease was evaluated by autoradiography after incorporation of tritiated thymidine. Neoplastic cells proliferated in the deepest layers of the epidermis suggesting a topographical control of their multiplication similar to that of the normal epidermis.     

Overexpression of transforming growth factor-β3 immunohistochemical staining in extramammary Paget's disease, but downregulated expression in Bowen's disease

BACKGROUND: The role of transforming growth factor-beta (TGF-beta) in carcinogenesis is complex, with some reports indicating a tumor inhibition role and others indicating a tumor promotion role. In particular, TGF-beta3 is thought to play a key role in controlling epithelial homeostasis. Immunopositive p53 has been demonstrated in a variety of human malignant tumors and its role in oncogenesis and tumor progression is thought to be important. Extramammary Paget's disease (EPD) and Bowen's disease are skin cancers of unknown histogenesis. OBJECTIVE: To clarify the role of TGF-beta3 and p53 in EPD and Bowen's disease and to better understand the origin of these disorders. METHODS: Specimens were obtained from 12 patients with EPD and 12 patients with Bowen's disease seen at our clinic between 1993 and 2000. TGF-beta3 and p53 immunohistochemical staining was performed. RESULTS: In three of the 12 EPD patients and five of the 12 Bowen's disease patients, positive p53 staining was detected. In contrast, TGF-beta3 overexpression was detected in all EPD patients, whereas downregulated TGF-beta3 expression was detected in all Bowen's disease patients. CONCLUSIONS: The present data suggest different roles for TGF-beta3 in abnormal epidermal cells in EPD and Bowen's disease. Thus, TGF-beta3 expression may be modulated differently via a p53-dependent or -independent pathway in the pathogenesis of EPD and Bowen's disease. Moreover, high TGF-beta expression appears to be a useful indicator of tumor activity in EPD.     

High expression of Ki-67 and cyclin D1 in invasive extramammary Paget's disease

BACKGROUND: Invasive extramammary Paget's disease (EMPD) is commonly associated with a poor prognosis. Although early detection of micro invasion can improve the prognosis, diagnosis is not always straightforward in some EMPD cases. Several clinical studies have proposed mechanisms underlying the increased invasiveness of EMPD; however, molecular markers indicative of the invasiveness have yet to be well characterized. OBJECTIVE: The purpose of this study was to identify a reliable immunohistochemical marker for predicting the risk of invasion and metastasis in EMPD cases. METHODS: A total of 32 specimens from 23 primary EMPD cases were analyzed by immunohistochemical staining. In formalin-fixed, paraffin-embedded tissue sections, immunolabeling of tumor cells were scored by stain intensity on a four-tiered scale. Using antibodies against several tumor proliferation markers, such as Her2, p53, Ki-67, cyclin D1 and Bcl-2, we determined the correlation between the expression of these molecular markers and the types of EMPD lesions (in situ, invasive or metastatic). RESULTS: In contrast to Her2, p53 and Bcl-2, which are similarly expressed among different types of lesions, Ki-67 and cyclin D1 are expressed at significantly higher levels in invasive lesions than in situ lesions (P<0.01 and P<0.05, respectively). Furthermore, the mean of the sum of Ki-67 and cyclin D1 expression scores was significantly higher in invasive lesions, compared to the scores obtained for in situ lesions. In addition, the difference was more significant (P相似文献   

Differential expression of mucin core proteins and keratins in apocrine carcinoma, extramammary Paget's disease and apocrine nevus

Background:  Apocrine carcinomas are rare, the immunohistochemical characterizations that are incomplete. The purpose of this study was to determine the immunohistochemical characteristics of mucin core proteins and keratins in apocrine carcinoma, extramammary Paget's disease (EMPD) and apocrine nevus.
Methods:  We report four cases of apocrine carcinomas along with immunohistochemical analyses: (i) an axillary apocrine carcinoma with an apocrine nevus, (ii) an inguinal apocrine carcinoma, (iii) a vulvar apocrine carcinoma with EMPD and (iv) an axillary apocrine carcinoma with EMPD and an apocrine nevus.
Results:  The tumor cells of apocrine carcinomas, EMPD and apocrine nevi displayed a positive reaction to MUC-1 and CK7 and a negative reaction to CK20. Apocrine carcinomas had high molecular weight (HMW) cytokeratin(+)/CK5(+)/CK14(−)/MUC5AC(−), EMPD with underlying apocrine carcinoma had HMW cytokeratin(−)/CK5(−)/CK14(−)/MUCA5AC(−) and the apocrine nevi had HMW cytokeratin(+)/CK5(+)/CK14(+)/MUCA5AC(+).
Conclusion:  The immunohistochemical findings suggest that apocrine carcinomas, apocrine nevi and EMPD with underlying apocrine carcinomas are quite different, even though they are all derived from apocrine glands.     

Immunolabeling pattern of syndecan-1 expression may distinguish pagetoid Bowen's disease, extramammary Paget's disease, and pagetoid malignant melanoma in situ

The differential diagnosis of pagetoid cells within the epidermis rests primarily between pagetoid Bowen's disease (PBD), extramammary Paget's disease (EPD), and pagetoid malignant melanoma (MIS) in situ. Although morphologic clues are often helpful in differentiating these lesions, the use of immunohistochemistry is often necessary to arrive at the correct diagnosis. Syndecan-1 is a cell-surface proteoglycan that mediates adhesion between cells and the extracellular matrix, and between cells themselves. Twenty-two cases of PBD, four cases of intraepidermal EPD, and 13 cases of MIS were examined for syndecan-1 immunoreactivity. Cell-membrane syndecan-1 immunoreactivity was evident in PBD, cytoplasmic syndecan-1 immunoreactivity was evident in EPD, whereas immunoreactivity for syndecan-1 was not present in MIS. The patterns of syndecan-1 immunoreactivity in these lesions may be a useful adjunct in the differentiation of PBD, EPD, and MIS.     

Colocalization of basic fibroblast growth factor and CD44 isoforms containing the variably spliced exon v3 (CD44v3) in normal skin and in epidermal skin cancers

Previous in vitro studies have shown CD44 isoforms containing the alternatively spliced exon v3 (CD44v3) to be modified with heparan sulphate (HS) and to bind HS-binding basic fibroblast growth factor (bFGF). Here, we demonstrate that exogenously added bFGF is also bound in vivo by CD44v3-positive keratinocytes in normal skin and by tumour cells in basal cell carcinoma and squamous cell carcinoma (SCC), two skin cancers of keratinocyte origin. bFGF binding and CD44v3 expression were colocalized in cultured human normal keratinocytes (HNK) and on the SCC cell line A431. By contrast, benign or malignant tumours of melanocyte origin failed to express CD44v3 and bound no bFGF. The bFGF binding to normal or transformed keratinocytes in vivo and in vitro was dependent on HS modification, as it was completely eliminated by pretreatment with heparitinase or by blocking with free heparin, whereas chondroitinase had no effect. In addition, specific removal of CD44v3 by antibody-induced shedding also diminished bFGF binding to keratinocytes. Furthermore, bFGF stimulated the proliferation of CD44v3-positive HNK and A431 in a dose-dependent fashion. This bFGF effect was again completely abolished by heparitinase or free heparin, but not by chondroitinase. In aggregate, our results suggest that a function of HS-modified CD44 isoforms such as CD44v3 in skin is to present the HS-binding growth factor bFGF, thereby stimulating the proliferation of normal or transformed keratinocytes.     

Serum cytokeratin 19 fragment 21-1 and carcinoembryonic antigen combination assay as a biomarker of tumour progression and treatment response in extramammary Paget disease

Extramammary Paget's disease (EMPD) is a rare skin cancer affecting the genitals and armpit regions. EMPDs occur mainly in Caucasian women and Asian men over the age of 60, in less than 0.6 per 100,000 people. Basic treatment is excision (removal) by operation, yet metastasis, meaning that it has spread, is seen in around 10% of patients. If the cancer is spreading, it is really important to detect this and start treatment as early as possible, since in late stages the disease can be hard to treat. A biomarker, or marker, is a molecule found in blood, different levels of which correspond with how well the body responds to a treatment, or to how the disease will progress. Carcinoembryonic antigen (CEA) and cytokeratin 19 fragment 21-1 (CYFRA 21-1) are both biomarkers for certain other cancers, and it has been suggested that they might also be markers for monitoring tumour progression in EMPD; however, neither the accuracy of, nor correlation between, these markers have been examined in EMPD patients. This study from Japan aimed to find out the usefulness and relationship of CEA and CYFRA21-1 levels in blood of EMPD patients in various progression states of the disease. A total of 30 EMPD cases were included in this study. In all early-stage patients, CEA and CYFRA were within normal levels. In advanced-stage patients, CEA and CYFRA were elevated in 79% and 63%, respectively. Either CEA or CYFRA was found to be elevated in 95% of the advanced patients, indicating that a certain number of patients have raised levels of only one of the markers. In addition, both of the markers also correlated well with the treatment responses in all patients. This study revealed that examining both CEA and CYFRA may help to detect advanced-stage EMPD patients, and that they are useful for monitoring treatment responses.