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Tenascin (TN) is an extracellular matrix glycoprotein expressed in areas of epithelial-mesenchymal interactions during embryogenesis and in neoplasia. We studied the expression of TN in a series of 35 squamous cell invasive carcinomas of the larynx, 13 in situ carcinomas, 41 cases of dysplasia, 10 papillomas and 18 cases of keratosis using the monoclonal antibody TN2 on paraffin-embedded tissue. TN expression was correlated with the expression of fibronectin, CD44 and cathepsin D (CD) proteins, with the proliferation indices Ki-67 and proliferating cell nuclear antigen (PCNA) as well as with conventional clinicopathological variables. Malignant tumours showed a significantly greater stromal TN staining than benign lesions. In invasive carcinomas, the immunoreactivity was statistically higher than that in situ (P=0.01), dysplastic lesions (P<0.0001), papillomas (P=0.004) and keratosis (P<0.0001). A statistically significant difference of TN expression between in situ and dysplastic lesions was observed (P=0.001). In invasive lesions, TN expression was statistically correlated with CD44 expression (P=0.02) and a trend for correlation with CD of tumour cells and fibronectin expression was found (P=0.06 and P=0.09, respectively). The relationship of TN expression with the histological grade and the proliferative activity was insignificant. In conclusion, stromal TN expression may be involved in the complex mechanism of development of laryngeal lesions and may help to predict the risk of progression of pre-cancerous lesions to cancer. [ABSTRACT FROM AUTHOR]

Metallothionein (MT) is a low-molecular-weight cysteine-rich protein, which has the ability to bind and sequestrate heavy metal ions. Synthesis of MT is induced in a variety of tissues by these metal ions, as well as by endogenous factors such as glucocorticoids, interferon, interleukin-1 and vitamin D. Several lines of evidence show that MT may play a role in carcinogenesis. In this study MT expression was detected immunohistochemically, using a monoclonal antibody (E9) against a conserved epitope of I and II isoforms, in a series of 63 cases of urothelial carcinomas of the urinary bladder. Correlation between MT expression and HLA-DR antigen expression, p53, proliferation indices (PCNA and MIBI) as well as the various clinicopathological parameters, such as age, sex, squamous metaplasia, tumor grade, stage and recurrence were studied. In a semiquantitative analysis MT expression (> 10% of neoplastic cells) was observed in 12.7%, focal MT positivity in 11.1% and almost completely lack of MT expression in 76.2% of tumors. The incidence of MT expression was significantly higher (p=0.0002) in cases with high pathological tumor grades. MT values were significantly correlated with tumor stage (p=0.0009). A statistically significant positive correlation between MT expression and the HLA-DR antigen expression (p=0.001) was also detected. The data suggested that MT expression was correlated with a more aggressive behavior in urothelial bladder cancer.

Expression of bcl-2 protein was investigated and correlated with Bax, p53 and Rb proteins, c-erbB-2, EGFR and the proliferation indices PCNA, Ki-67 and MIB1 as well as with the conventional clinicopathological parameters in 95 cases for breast cancer tissue and 20 cases of benign hyperplastic lesions. Bcl-2 and Bax proteins immunoreactivity was detected in normal, hyperplastic and neoplastic breast epithelium. Expression of the bcl-2 protein was detected in 40% of carcinomas (> 10% positive neoplastic cells) and 85.2% of the benign hyperplastic lesions. Bax protein expression was detected in 8.1% of the carcinomas and 5.3% in the hyperplastic group. Rb and p53 proteins were detected in 75.5% and 45.5% of carcinomas. No relationship was observed between bcl-2 expression and patient's age, tumour size, tumour type and grade, lymph node status, Rb protein expression and proliferation indices. However, a strong positive relationship was detected between bcl-2 and Bax (p = 0.008), estrogen (ER) (p = 0.007) and progesterone receptors' (PgR) status (p = 0.0003). An inverse correlation with p53 protein (p = 0.004) was detected. Furthermore, a strong correlation was also observed between pRb and p53 (p = 0.001). The results indicate that in breast cancer bcl-2 protein expression may be under hormonal control. Since the expression is bcl-2 protein was inversely correlated with p53 protein expression, we suggest that bcl-2 may be related with favourable outcome in breast cancer.

Metallothioneins (MTs) are a group of ubiquitous low-molecular-weight proteins essential for the protection of cells against heavy metal ion toxicity. The immunohistochemical expression of MT was studied by immunohistochemistry using a monoclonal antibody (E9) against a conserved epitope of I and II isoforms in a series of 89 endometrial carcinomas, 34 cases of hyperplasia, and 32 samples of normal endometrium. In secretory phase endometrium, extensive MT expression was detected in most cases (92.4%). In contrast, MT immunoreactivity was confined to small foci in 22.2% of proliferative phase cases. The MT values in normal endometrium were inversely correlated with oestrogen receptor (ER) content (p<0.0001), progesterone receptor (PgR) content and with PCNA (p<0.0001) and MIB1 (p=0.001) scores. In hyperplastic lesions, MT expression was detected only in 3.3% of cases, while in the group of carcinomas it was observed in 23.1%. A statistically significant difference of MT expression was observed between carcinomas and simple hyperplasias (p=0.03). In carcinomas, MT expression was positively correlated with grade (p=0.0065), MIB1 (p=0.022), and p53 (p=0.006) expression, and inversely with PgR (p=0.03). A trend of inverse correlation between MT and ER receptor was also detected (p=0.07). These data suggest that MT expression seems to be under hormonal control in normal endometrium; that it may modify p53 expression; and that it could be used as an additional biological marker indicating aggressive behaviour in endometrial lesions., (Copyright 2000 John Wiley & Sons, Ltd.)

Tenascin (TN) is an extracellular matrix glycoprotein expressed in areas of epithelial-mesenchymal interactions during embryogenesis and in neoplasia. We studied the expression of TN in a series of 35 squamous cell invasive carcinomas of the larynx, 13 in situ carcinomas, 41 cases of dysplasia, 10 papillomas and 18 cases of keratosis using the monoclonal antibody TN2 on paraffin-embedded tissue. TN expression was correlated with the expression of fibronectin, CD44 and cathepsin D (CD) proteins, with the proliferation indices Ki-67 and proliferating cell nuclear antigen (PCNA) as well as with conventional clinicopathological variables. Malignant tumours showed a significantly greater stromal TN staining than benign lesions. In invasive carcinomas, the immunoreactivity was statistically higher than that in situ (P=0.01), dysplastic lesions (P<0.0001), papillomas (P=0.004) and keratosis (P<0.0001). A statistically significant difference of TN expression between in situ and dysplastic lesions was observed (P=0.001). In invasive lesions, TN expression was statistically correlated with CD44 expression (P=0.02) and a trend for correlation with CD of tumour cells and fibronectin expression was found (P=0.06 and P=0.09, respectively). The relationship of TN expression with the histological grade and the proliferative activity was insignificant. In conclusion, stromal TN expression may be involved in the complex mechanism of development of laryngeal lesions and may help to predict the risk of progression of pre-cancerous lesions to cancer.

The immunohistochemical Cathepsin D (CD) expression of tumour and stromal cells was investigated in a series of 93 human colorectal adenocarcinomas and 22 adenomas with the intention to evaluate its prognostic significance and its contribution in the metastatic potential of colorectal cancer. CD expression was correlated with the expression of extracellular matrix components (collagen type IV, laminin and fibronectin), p53 protein, pRb, bcl-2, c-erbB-2, EGFR, proliferation indices (Ki-67, PCNA) as well as with other conventional clinicopathological features. CD expression (> 10% of positive tumour cells) was observed in 60.2% of carcinomas and in 72.7% of adenomas. Stromal CD expression was detected in all cases. A statistically significant positive correlation between neoplastic cells CD and stromal cells CD (SCCD) was observed in both carcinomas and adenomas. Cancer cells CD (CCCD) was positively correlated with collagen type IV and pRb expression as well as with PCNA score. In carcinomas, SCCD expression was statistically correlated with p53 protein and pRb expression and a trend for correlation with PCNA score was found. These data suggest that Cathepsin D of cancer and stromal cells, especially in combination with other markers, may provide more information about the biological behaviour of colorectal cancer.

Matrix metalloproteinases (MMPs) are a group of enzymes thought to be responsible for both normal connective tissue matrix remodelling and accelerated breakdown associated with tumour development. The current study aimed to investigate the immunohistochemical expression of matrix metalloproteinase 3 (MMP-3, stromelysin-1) in correlation with the expression of Basement Membrane (BM) antigen (type IV collagen, laminin), fibronectin, cathepsin D, p53, c-erbB-2, proliferative activity (Ki-67, PCNA), steroid receptor content as well as to the other conventional clinicopathological parameters in breast cancer. This study was performed on a series of frozen and paraffin sections from 84 breast cancer specimens by immunohistochemistry using the monoclonal antibody MMP-3 (Ab-1). Stromelysin-1 (ST1) was observed in about 10% of epithelial cells in the control groups (cases of fibrocystic and benign proliferative breast disease), while expression (> 10% of expression) was detected in 89.7% of tumours. The expression of ST1 in carcinoma cells was strongly associated with its presence in the stroma (p < 0.001). A significantly positive correlation was found between ST1 expression, and p53 tumour suppressor gene product (p = 0.004), and a relationship with c-erbB-2 protein and progesterone receptor status was also indicated. These findings suggest that ST1 expression in breast cancer tissue is irrespective of the expression of the extracellular matrix component, the proteolytic enzyme cathepsin D and the growth fraction of the tumour, and that it could be a potential new prognostic marker in breast cancer.

Enchondroma of the scaphoid has been rarely reported. A young male manual worker presented with a pathologic fracture on the lesion. It was successfully managed with a vascularized bone graft from the dorsum of the distal radius.