Immunohistochemical study of desmosomes in oral squamous cell carcinoma: correlation with cytokeratin and E-cadherin staining, and with tumour behaviour

Shinohara, Masanori; Hiraki, Akimitsu; Ikebe, Tetsuro; Nakamura, Seiji; Kurahara, Shinichi; Shirasuna, Kanemitsu; Garrod, David R.

doi:10.1002/(sici)1096-9896(199804)184:4<369::aid-path1236>3.0.co;2-l

Cited by 90 publications

(80 citation statements)

References 33 publications

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“…We are not aware of any ultrastructural studies of desmosomes in AKs. Our present results are also similar to our findings for desmosomal staining in oral SCCs and transitional cell carcinoma, in which reduction in staining for Dsg and other desmosomal components has been found to be associated with invasive and/or metastatic behaviour (Conn et al, 1990;Hiraki et al, 1996;Shinohara et al, 1997). They contrast, however, with our findings for colorectal carcinoma, in which no reduction in desmosomal staining was detected in association with low differentiation status or metastasis.…”

Section: Discussionsupporting

confidence: 90%

Immunohistochemical staining for desmogleins 1 and 2 in keratinocytic neoplasms with squamous phenotype: actinic keratosis, keratoacanthoma and squamous cell carcinoma of the skin

Krunic

Garrod²,

Madani³

et al. 1998

Br J Cancer

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Summary Desmosomes are intercellular junctions that have been shown to be down-regulated in certain types of carcinoma and that may play a role in suppression of invasion and metastasis. This paper describes an immunohistochemical study of three types of epidermal neoplasms with monoclonal antibody to desmoglein in order to determine how desmosomal staining correlates with the clinical, biological and histopathological features of these neoplasms. Actinic keratosis (AK) is the most common keratinocytic premalignant neoplasm that was reported to have a 10-20% rate of malignant transformation into squamous cell carcinoma (SCC). Keratoacanthoma (KA) is a benign neoplasm that involutes spontaneously after a few months of rapid growth. SCC is a malignant tumour capable of metastasis. Electron microscope studies of KA and SCC showed significantly reduced staining for desmosomes in SCC but not in KA. We have examined staining for desmoglein using the monoclonal antibody 33-3D, a mouse IgM monoclonal antibody, that recognizes the cytoplasmic domains of desmoglein (Dsg)1 and Dsg2 on frozen sections. Immunohistochemical staining of normal skin with this antibody revealed strong pericellular localization of the antigen, outlining the cell membranes of the keratinocytes. A series of 30 AKs, 12 KAs and 24 SCCs was stained immunohistochemically with 33-3D monoclonal antibody. All examined KAs showed extensive pericellular staining for Dsg. By contrast, juxtanuclear staining for Dsg was noted in 12 SCCs, and completely negative staining in seven SCCs. The five remaining SCCs showed focal pericellular staining for the Dsg marker. The most common finding in AK was focal pericellular staining for Dsg, with complete absence of staining in dysplastic areas (25 cases). In five cases negative pericellular staining in dysplastic areas was associated with juxtanuclear accumulation of the Dsg marker. A strong negative correlation between Dsg staining and degree of dysplasia was obtained. The Dsg pattern in KA is similar to normal epidermis and shows a clear difference between KA and SCC. AK has a limited loss of Dsg expression in a SCClike pattern that is congruent with its premalignant nature. As the stain works on frozen tissue, it may be helpful for rapid differentiation in selected cases in cutaneous oncology and Mohs micrographic surgery. This antibody may also have great potential for the detection of the effects of chemopreventive agents in skin cancer.

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Section: Discussionsupporting

confidence: 90%

Immunohistochemical staining for desmogleins 1 and 2 in keratinocytic neoplasms with squamous phenotype: actinic keratosis, keratoacanthoma and squamous cell carcinoma of the skin

Krunic

Garrod²,

Madani³

et al. 1998

Br J Cancer

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“…Immunohistochemical studies have shown that a loss of staining for desmosomal components correlates with invasive and metastatic potential in both transitional cell carcinoma (Conn et al, 1990) and squamous cell carcinoma (Harada et al, 1992;Hiraki et al, 1996;Shinohara et al, 1998). Transfection of the cDNA encoding desmosomal components into highly invasive cells inhibits their in vitro invasion of collagen gels (Tselepis et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

HOXD3 enhances motility and invasiveness through the TGF-β-dependent and -independent pathways in A549 cells

et al. 2002

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Homeobox genes regulate sets of genes that determine cellular fates in embryonic morphogenesis and maintenance of adult tissue architecture by regulating cellular motility and cell-cell interactions. Our previous studies showed that a speci®c member, HOXD3, when overexpressed, upregulates integrin b3 expression in human erythroleukemia HEL cells and lung cancer A549 cells, and enhances their motility and invasiveness. We performed a microarray study of over 7075 genes to determine the mechanisms underlying the HOXD3-enhanced motility and invasiveness in A549 cells. RT ± PCR-based tracking gene analyses highlighted a set of TGF-b-upregulated genes, which included matrix metalloproteinase-2, syndecan-1, CD44, and TGF-b-induced 68 kDa protein. Exogenous TGF-b also caused this pattern of upregulation in A549 cells and enhanced their migratory and invasive activity, con®rming the involvement of TGF-b signaling. However, HOXD3 reduced the expression of TGF-b-independent genes coding for desmosomal components such as desmoglein, desmoplakin and plakoglobin which are known to suppress tumor invasion and metastasis. These results suggest that HOXD3 enhances the invasive and metastatic potential of cancer cells through the TGF-b-dependent and -independent pathways.

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“…36,54 A decrease in both desmoplakins and desmoglein in oral squamous cell carcinomas was correlated with poor differentiation, invasiveness, and lymph node metastases. 55 Clearly, by itself the disturbance in desmosomal plaques does not lead to invasive properties of cells, because in the case of SILs, it was observed for noninvasive precancerous lesions. The assembly of desmosomes is believed to be dependent on E-cadherin and proper adherens junction formation 56 -58 and an intact actin and cytokeratin network.…”

Section: Discussionmentioning

confidence: 99%

Changing Roles of Cadherins and Catenins during Progression of Squamous Intraepithelial Lesions in the Uterine Cervix

Boer

Dorst²,

Krieken

et al. 1999

The American Journal of Pathology

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Uterine cervix represents a convenient model for the study of the gradual transformation of normal squamous epithelium via low-to high-grade squamous intraepithelial lesions (SILs). Because SIL , on the basis of the cytokeratins expressed , are thought to originate from the reserve cells , we analyzed whether SILs also show a reserve cell phenotype with respect to intercellular interactions. The changes in expression and subcellular localization of the components of the adherens junction and desmosomal complexes were investigated in normal , metaplastic , and premalignant cervical epithelium , as well as in cell cultures derived from these tissues. The results suggest that 1) during progression of SILs , E-cadherin is suppressed, with its role in cell-cell connections diminishing; 2) P-cadherin , in contrast , becomes the predominant cadherin in high-grade SILs; 3) the level of cellular ␣-catenin is dramatically decreased in high-grade SILs; 4) the level of ␤-catenin is decreased during progression of SILs , with plakoglobin suggestively becoming the predominant catenin mediating connection of cadherins to the cytoskeleton; 5) the assembly of desmosomes is affected during progression of SILs and is accompanied by a dramatically decreased expression for desmogleins and desmoplakins (I , II); and 6) expression of differentiation markers (involucrin , CK13) in high-grade SILs seems to be controlled by P-cadherin as opposed to E-cadherin in the normal tissue counterpart. We conclude that during development of cervical lesions substantial (

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Immunohistochemical study of desmosomes in oral squamous cell carcinoma: correlation with cytokeratin and E-cadherin staining, and with tumour behaviour

Cited by 90 publications

References 33 publications

Immunohistochemical staining for desmogleins 1 and 2 in keratinocytic neoplasms with squamous phenotype: actinic keratosis, keratoacanthoma and squamous cell carcinoma of the skin

Immunohistochemical staining for desmogleins 1 and 2 in keratinocytic neoplasms with squamous phenotype: actinic keratosis, keratoacanthoma and squamous cell carcinoma of the skin

HOXD3 enhances motility and invasiveness through the TGF-β-dependent and -independent pathways in A549 cells

Changing Roles of Cadherins and Catenins during Progression of Squamous Intraepithelial Lesions in the Uterine Cervix

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