The correlation between the expression of COX-2 and p53 protein in basal cell carcinoma (BCC) of eyelid and apoptosis was investigated. Specimens of BCC were collected from 40 cases (aged 28-68 y) at the Department of Pathology, Renmin Hospital of Wuhan University, and Department of Pathology, Zhongnan Hospital of Wuhan University during from 1999 to 2006. Five specimens of paracancerous tissues served as control group. Immunohistochemical staining was performed to detect the expression of COX-2 and p53 in the tissues. The average absorbance (A) and the average positive area rate of COX-2 and p53 protein were measured by image analysis. The positive area rate of COX-2 and p53 protein was analyzed by linear correlation analysis. It was found that COX-2 and p53 proteins were highly expressed in BCC of eyelid, and weakly expressed in paracancerous tissues. Image analysis revealed that the expression of COX-2 and p53 proteins in BCC of eyelid was significantly higher than that in paracancerous tissues (P<0.01). Spearman rank correlation analysis demonstrated a positive correlation between the expression of COX-2 and p53 (r=0.113, P=0.421). It was concluded that COX-2 can increase the expression of p53 protein, therefore suppressing apoptosis.
Apoptosis ; Carcinoma, Basal Cell/*metabolism ; Cyclooxygenase 2/*metabolism ; Eyelid Neoplasms/*metabolism ; Tumor Suppressor Protein p53/*metabolism

Impaired regulation of apoptosis is known to be associated with the development of various cancers, and Fas/Fas-ligand (FasL) is known to play an important role in apoptosis. CD40 is a cell surface receptor, which when ligated modulates apoptosis in some cell types. The expressions of CD40 and FasL were examined in 10 normal skins, 7 Bowen's disease skins, 10 squamous cell carcinomas (SCCs) and 12 basal cell carcinomas (BCCs) immunohistochemically. In the normal epidermis, CD40 was more highly expressed in the keratinocytes of the squamous cell and granular layers than in those of the basal layer, and FasL expression was observed in the cell membrane of keratinocytes at the basal and squamous cell layers. CD40 expression was significantly higher in SCCs than in normal or Bowen's disease skin, while FasL expression was significantly higher in Bowen's disease than in SCCs. BCCs expressed the lowest levels of CD40 and FasL. These results suggest that altered CD40 and FasL expression may be related with the progression of SCC, and the marked reduced expression of CD40 and FasL may explain the biologic behavior of BCCs.
Antigens, CD40/*metabolism ; Bowen's Disease/*metabolism ; Carcinoma, Basal Cell/*metabolism ; Carcinoma, Squamous Cell/*metabolism ; Human ; Membrane Glycoproteins/*metabolism ; Reference Values ; Skin/metabolism ; Skin Neoplasms/*metabolism

OBJECTIVETo investigate the expression of promyelocytic leukaemia (PML) protein of PML protein in Bowen's disease (BD), skin squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) and explore the role of PML in the pathogenesis of these diseases.

METHODSPML protein in normal skin tissues and lesions of Bowen's disease, SCC and BCC were detected with immunohistochemistry.

RESULTSNormal skin tissues did not express PML protein. In BCC, PML showed rather low expressions in the skin lesions (8.69% in cell nuclei and 4.35% in cytoplasm). The lesions in BD and SCC (grade I and II) showed obvious overexpression of PML protein in the cell nuclei and cytoplasm, and its expression in the cell nuclei of these lesions was significantly higher than that in grade III-IV SCC.

CONCLUSIONPML protein may play an important role in the early stage of SCC, and its overexpression may contribute to the carcinogenesis and metastasis of SCC.

Adult ; Aged ; Bowen's Disease ; metabolism ; pathology ; Carcinoma, Basal Cell ; metabolism ; pathology ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Female ; Humans ; Male ; Middle Aged ; Nuclear Proteins ; metabolism ; Promyelocytic Leukemia Protein ; Skin Neoplasms ; metabolism ; pathology ; Transcription Factors ; metabolism ; Tumor Suppressor Proteins ; metabolism

BACKGROUNDGlycoprotein non-metastatic melanoma protein B (GPNMB) plays an important role in the pathogenesis of inflammatory and malignant diseases. We investigated the expression of GPNMB in benign and malignant skin diseases.

METHODSTissue microarray was performed in the skin tissues of 102 cases including malignant melanoma (MM), squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and benign dermatosis. The expression of GPNMB in the tissues was detected by immunohistochemistry. Twenty cases of normal skin and adjacent neoplastic normal skin tissues were selected as controls.

RESULTSGPNMB was positively stained in skin malignancies (38/50, 76%), which was significantly higher than that in the control and the benign skin tissues (P = 0.001 and < 0.001 respectively). GPNMB was positively stained in MM (13/15, 87%) and SCC (16/20, 80%) (P < 0.001). Significant higher expression of GPNMB was observed in patients aged ≥ 65 years than those less than 65 years (n = 11 and n = 9 respectively, P = 0.027). No significant difference of the expression rates was observed between normal control and BCC; however, stronger intensity was detected in the latter. Negative or weak expression was observed in the controls.

CONCLUSIONOver-expression of GPNMB correlated strongly and might play an important role in the pathogenesis of MM and SCC.

Adolescent ; Adult ; Aged ; Carcinoma, Basal Cell ; metabolism ; Carcinoma, Squamous Cell ; metabolism ; Female ; Humans ; Immunohistochemistry ; Male ; Melanoma ; metabolism ; Membrane Glycoproteins ; metabolism ; Middle Aged ; Skin ; metabolism ; pathology ; Skin Diseases ; metabolism ; Skin Neoplasms ; metabolism ; Tissue Array Analysis ; methods ; Young Adult

Hedgehog was first described in Drosophila melanogaster by the Nobel laureates Eric Wieschaus and Christiane Nüsslein-Volhard. The hedgehog (Hh) pathway is a major regulator of cell differentiation, proliferation, tissue polarity, stem cell maintenance, and carcinogenesis. The first link of Hh signaling to cancer was established through studies of a rare familial disease, Gorlin syndrome, in 1996. Follow-up studies revealed activation of this pathway in basal cell carcinoma, medulloblastoma and, leukemia as well as in gastrointestinal, lung, ovarian, breast, and prostate cancer. Targeted inhibition of Hh signaling is now believed to be effective in the treatment and prevention of human cancer. The discovery and synthesis of specific inhibitors for this pathway are even more exciting. In this review, we summarize major advances in the understanding of Hh signaling pathway activation in human cancer, mouse models for studying Hh-mediated carcinogenesis, the roles of Hh signaling in tumor development and metastasis, antagonists for Hh signaling and their clinical implications.
Animals ; Antineoplastic Agents ; therapeutic use ; Basal Cell Nevus Syndrome ; drug therapy ; metabolism ; Carcinoma, Basal Cell ; drug therapy ; metabolism ; Cell Differentiation ; Cerebellar Neoplasms ; drug therapy ; metabolism ; Hedgehog Proteins ; antagonists & inhibitors ; metabolism ; Humans ; Medulloblastoma ; drug therapy ; metabolism ; Models, Animal ; Neoplasms ; drug therapy ; metabolism ; Patched Receptors ; Receptors, Cell Surface ; genetics ; metabolism ; Signal Transduction ; drug effects ; Skin Neoplasms ; drug therapy ; metabolism

OBJECTIVETo investigate the clinicopathologic and immunohistochemical features as well as the differential diagnoses of the solid variant of mammary adenoid cystic carcinoma with basaloid features.

METHODSClinical and pathological data were collected in four cases of the solid variant of mammary adenoid cystic carcinoma with basaloid features, and microscopic pathological examination and immunohistochemistry EnVision method were performed. The relevant literature was also reviewed.

RESULTSThe four patients were female, with age ranged from 46 - 65 years old (average 56 years) and the maximum tumor diameter ranged from 1.5 to 2.5 cm. Microscopically, the tumors exhibited a predominantly solid architecture with a myxoid or hyalinized stroma. The tumor cells showed moderate to marked nuclear atypia, and a basaloid appearance with scanty cytoplasm and inconspicuous nucleoli, and ≥ 5 mitotic figures per 10 high power fields. Glandular space embedded within tumor islands could be noticed. These spaces were genuine glandular structures and the cells lining these true glandular lumens had more abundant and eosinophilic cytoplasm. Pseudoglandular spaces of cribriform pattern or variable shape were also occasionally seen, and these cysts contained homogenous eosinophilic material. Focal necrosis was found. All cases were negative for ER, PR and HER2. Immunohistochemical staining for CK5/6, CK7 and CK14 was positive in the genuine glandular structures. All cases were positive for CD10, but also positive with varying intensity from weak to strong for vimentin and CD117. Staining for Ki-67 in three patients showed 10% - 50% positive.

CONCLUSIONSThe solid variant of mammary adenoid cystic carcinoma with basaloid features is a histologically distinctive and also a rare subset of the mammary adenoid cystic carcinoma. Awareness of its pathological features can help with the diagnosis as well as differential diagnosis. More cases are still needed for accurately assessing the prognosis of this particular tumor.

Aged ; Breast Neoplasms ; metabolism ; pathology ; surgery ; Carcinoma, Adenoid Cystic ; metabolism ; pathology ; surgery ; Carcinoma, Basal Cell ; metabolism ; pathology ; surgery ; Carcinoma, Ductal, Breast ; metabolism ; pathology ; Carcinoma, Small Cell ; metabolism ; pathology ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; Keratin-14 ; metabolism ; Keratin-5 ; metabolism ; Keratin-7 ; metabolism ; Mastectomy ; methods ; Middle Aged ; Proto-Oncogene Proteins c-kit ; metabolism ; Vimentin ; metabolism

Adult ; Arm ; Carcinoembryonic Antigen ; metabolism ; Carcinoma, Basal Cell ; pathology ; Carcinoma, Skin Appendage ; metabolism ; pathology ; surgery ; Diagnosis, Differential ; Head and Neck Neoplasms ; metabolism ; pathology ; surgery ; Humans ; Male ; Middle Aged ; Mucin-1 ; metabolism ; Skin Neoplasms ; metabolism ; pathology ; surgery

OBJECTIVETo investigate the effect of stat3 phosphorylation and p53 expression on human epidermal non-melanoma cutaneous tumours.

METHODSImmunohistochemistry technique was employed to measure the expression of p-stat3 and p53 protein in skin tissue from 30 cases of skin squamous cell carcinoma (SCC), 20 cases of basal cell carcinoma (BCC), 20 cases of seborrhoeic keratosis (SK) and 20 normal subjects.

RESULT(1) p-stat3 protein was abnormally increased in SCC and BCC as compared with normal skin and SK. Expression of p-stat3 in SCC was also significantly higher than that in BCC. (2) Expression of p-stat3 was higher in poorly-differentiated cancers than that in well-differentiated cancers in SCC. The positive rate of p-stat3 expression was correlated with the depth of tumor invasion, but not with tumor size. (3) There was no p53 protein expression on normal skin and SK, it was significantly upregulated in SCC and BCC. In SCC, the intensity of p53 expression was associated with tumor differentiation. There was no correlation between the positive rate of p53 expression and the depth of tumor invasion, whereas the positive rate of p53 expression was correlated with the sun-exposure area. (4) There existed positive correlation between the expression intensity of p-stat3 and p53 in SCC (r=0.641, P<0.05).

CONCLUSION(1) The overexpression of p-stat3 may play an important role in the development of epidermal tumors. (2) The abnormal activation of stat3 may be related to metastatic potentials in SCC. (3) Both p53 gene and stat3 may contribute to the pathogenesis of skin SCC.

Carcinoma, Basal Cell ; chemistry ; pathology ; Carcinoma, Squamous Cell ; chemistry ; pathology ; DNA-Binding Proteins ; metabolism ; Humans ; Immunohistochemistry ; Keratosis, Seborrheic ; metabolism ; Phosphorylation ; STAT3 Transcription Factor ; Skin ; chemistry ; Skin Neoplasms ; chemistry ; pathology ; Trans-Activators ; metabolism ; Tumor Suppressor Protein p53 ; analysis

Adenoma ; metabolism ; pathology ; Biomarkers ; metabolism ; Biomarkers, Tumor ; metabolism ; Carcinoma, Basal Cell ; metabolism ; pathology ; Diagnosis, Differential ; Humans ; Hyperplasia ; Immunohistochemistry ; Male ; Prostate ; metabolism ; pathology ; Prostatic Hyperplasia ; metabolism ; pathology ; Prostatic Neoplasms ; metabolism ; pathology

Adult ; Aged ; Biomarkers, Tumor ; metabolism ; Carcinoma, Basal Cell ; metabolism ; pathology ; surgery ; Humans ; Keratin-5 ; metabolism ; Keratins ; metabolism ; Male ; Membrane Proteins ; metabolism ; Neoplasm Recurrence, Local ; Prostate ; metabolism ; pathology ; surgery ; Prostatectomy ; Prostatic Neoplasms ; metabolism ; pathology ; surgery