bcl-2 expression in epidermal keratinocytic diseases

Nakagawa, Miho; Yamamura, Masao; Maeda, Miyoko; Ichihashi, Masamitsu

doi:10.1002/1097-0142(19940915)74:6<1720::aid-cncr2820740613>3.0.co;2-t

Cited by 118 publications

(80 citation statements)

References 15 publications

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“…We agree with Waring et al (1996) that multiple differences exist between KAs and SCCs, and that the existence of 'metastasizing KAs' is not absolutely convincing (Krunic et al, 1996). On the other hand, focal loss of Dsg staining in AKs is similar to that observed in SCCs (Krunic et al, 1996) and, together with bcl-2 positivity (Nakagawa et al, 1994) as well as high FAL (Rehman et al, 1994, underlines the premalignant nature of this neoplasm. However, this does not explain the long-term low incidence of invasive growth and the 20% regression rate observed in this neoplasm (Marks et al, 1988;Schwartz, 1996).…”

Section: Discussionsupporting

confidence: 70%

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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: 70%

“…In the process of maturation the bcl-2 activity disappears, consistent with the initiation of apoptosis at involution of KAs. Bcl-2 positivity was also detected in hypertrophic AKs and was confined to the atypical keratinocytes (Nakagawa et al, 1994).…”

Section: Discussionmentioning

confidence: 94%

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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“…In general, the data obtained in the present study are in agreement with those of several other authors who evaluated the expression of PCNA, p53, bax and bcl-2 in addition to other proteins related to cell proliferation and apoptosis in oral lichen planus (21,26,(29)(30)(31)(32). For these authors, the alterations in the expression of these proteins were a strong indicator of the potential for malignant transformation of oral lichen planus, as these proteins participate actively in oral carcinogenesis.…”

Section: Discussionsupporting

confidence: 54%

Immunohistochemical expression of PCNA, p53, bax and bcl-2 in oral lichen planus and epithelial dysplasia

et al. 2009

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A b s t r a c t : T h e p o t e n t i a l fo r m a l i g n a n t transformation of oral lichen planus is still controversial.The expression of proteins related to cell proliferation and apoptosis in oral lichen planus and epithelial dysplasia was analyzed to evaluate the true potential for malignant transformation of this disease. Twentyfour cases of each lesion were subjected to the streptoavidin-biotin technique for identifying the immunohistochemical expression of PCNA, p53, bax, and bcl-2 proteins. Of the 24 cases of oral lichen planus, 14 (58.33%) were positive for PCNA, 10 (41.67%) for p53, 4 (16.67%) for bcl-2 and 12 (50%) for bax, whereas of the 24 cases of epithelial dysplasia, 20 (83.33%) were positive for PCNA, 10 (41.67%) for p53, 6 (25%) for bcl-2, and 20 (83.33%) for bax. Chi-squared test showed no statistically significant differences between the expression of p53 and bcl-2 in oral lichen planus and epithelial dysplasia, regardless of the grade (P > 0.05). However, the expression of PCNA and bax was significantly increased in epithelial dysplasia (P < 0.05). The results of this study showed that alterations in expression of these proteins are observed in oral lichen planus and epithelial dysplasia, suggesting the potential for malignant transformation in both lesions. IntroductionOral lichen planus is a chronic inflammatory disease of unknown cause, and its potential for malignant transformation is a subject of much controversy (1). Since the first case was reported in 1910, several studies have suggested that patients with oral lichen planus are at an increased risk of developing cancer (1-7).However, many authors believe that there is insufficient data to prove an association between oral lichen planus and cancer. For these authors, most cases of malignant transformation are the result of errors in the initial diagnosis of the disease (1,8-13).The true potential for malignant transformation of oral lichen planus can be evaluated by analyzing the expression of proteins related to cell proliferation and apoptosis, as alterations in the expression of these proteins are essential for carcinogenesis (14)(15)(16)(17)(18)(19).Therefore, the aim of this study was to evaluate the immunohistochemical expression of PCNA, p53, bax and bcl-2 proteins in oral lichen planus and epithelial dysplasia in order to explain the controversy regarding the potential for malignant transformation of oral lichen planus and emphasize the importance of long-term follow-up of patients with this disease. Materials and MethodsThe samples used in this study consisted of 24 cases of oral lichen planus and 24 cases of epithelial dysplasia (4 mild, 12 moderate, 8 severe) obtained from the records of

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“…On the other hand, the pattern of expression of Bcl-2 protein in normal skin remains controversial. In fact, we found lack of keratinocyte Bcl-2 positivity as previously reported by some authors (27)(28), but our results are not consistent with findings of other authors, who demonstrated Bcl-2 immunoreactivity in normal basal keratinocytes (12,29). The expression of Bax protein, which is the product of a protooncogene of the Bcl-2 family acting as death agonist (30), has also been investigated, giving negative findings.…”

Section: Pi: Steven-johnson Syndrome (Sjs) Versus Healthy Skin (Hs) Psupporting

confidence: 54%

Immunohistochemical Expression of Apoptotic Markers in Drug-Induced Erythema Multiforme, Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

Marzano

Frezzolini

Caproni

et al. 2007

Int J Immunopathol Pharmacol

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Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are considered to be severity variants of the same disease, which is almost always associated with drug intake. In contrast, erythema multiforme (EM) is a disorder regarded as only rarely caused by drugs. Keratinocyte apoptosis has been shown to play an important part in the pathogenesis of SJS and TEN, whilst its role in EM remains controversial. To determine the expression of apoptosis-associated molecules Fas, Fas ligand (FasL), BcI-2 and Bax in the above disorders, an immunohistochemical anatysis was performed. We studied both lesional skin from thirty patients having drug-induced EM and 5 cases classified within the SJS/TEN spectrum and normal skin samples. We found a keratinocyte overexpression of Fas antigen, an important molecule mediating apoptosis, not only in SJS and TEN but also in EM. Another noteworthy finding was the strong expression of BcI-2, a protein known as blocking apoptosis, along the basal layer and in the dermal infiltrate both in SJS/TEN and in EM. Taken together, these findings suggest that Fas-dependent keratinocyte apoptosis may playa part in the pathogenesis of both SJS/TEN and EM. Fas-mediated cell death may be partially suppressed by the BcI-2 protein.Until recently, most textbooks of medicine considered erythema multi forme (EM) to be a spectrum of disorders that included EM majus, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). A few years ago, some authors suggested that EM majus is different from SJS and TEN, not only in severity but also in the pattern and distribution of the skin lesions, whereas SJS and TEN are only severity variants of a single entity (1-4).This last is almost always associated with drug intake, whilst EM, both in its majus variant and in the form so-called minor, is predominantly caused by preceding infections, notably with herpes simplex virus (HSV), and only rarely by drugs.

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bcl-2 expression in epidermal keratinocytic diseases

Cited by 118 publications

References 15 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

Immunohistochemical expression of PCNA, p53, bax and bcl-2 in oral lichen planus and epithelial dysplasia

Immunohistochemical Expression of Apoptotic Markers in Drug-Induced Erythema Multiforme, Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

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