Kaori Kayano

Activation of pro-MMP-2 mediated by MT1-MMP in human salivary gland carcinomas: possible regulation of pro-MMP-2 activation by TIMP-2

Matrix metalloproteinases (MMPs), a family of extracellular matrix‐degrading enzymes, are considered to play important roles in cancer invasion and metastasis. The present study examined the production levels of eight different MMPs (MMP‐1, 2, 3, 7, 8, 9 and 13, and MT1‐MMP) and two tissue inhibitors of metalloproteinases (TIMP‐1 and 2) in homogenates of human salivary gland carcinomas [mucoepidermoid carcinomas (MECs), adenoid cystic carcinomas (ACCs), and adenocarcinomas (ADEs)] and non‐neoplastic control salivary glands using sandwich enzyme immunoassay systems. The levels of MMP‐1, MMP‐2, MMP‐13, MT1‐MMP, and TIMP‐1 were significantly higher in the carcinoma samples than in the controls (p < 0.05). Gelatin zymography demonstrated that the activation ratio of the MMP‐2 zymogen (pro‐MMP‐2) was significantly higher in the carcinomas than in the controls (p < 0.05). In addition, the activation ratio in MECs was significantly higher than that in ACCs or ADEs (p < 0.01) and also correlated with histological grade and lymph node metastasis in MECs (p < 0.05), whereas the ratio showed no such correlation in ACCs or ADEs. Although the production levels of pro‐MMP‐2 and MT1‐MMP were similar among these carcinoma groups, TIMP‐2 levels were significantly higher in ACCs and ADEs than in MECs (p < 0.01). In carcinoma samples, the pro‐MMP‐2 activation ratio correlated directly with the MT1‐MMP/TIMP‐2 ratio (r = 0.736, n = 23; p < 0.01). Immunohistochemistry and in situ zymography demonstrated localization of MMP‐2, MT1‐MMP, and TIMP‐2 to carcinoma cells, but only in MECs did carcinoma cell nests exhibit gelatinolytic activity, which was inhibited by 1,10‐phenanthroline. These results suggest that enhanced activation of pro‐MMP‐2 mediated by MT1‐MMP is implicated in the invasion and metastasis of MECs and that TIMP‐2 may regulate pro‐MMP‐2 activation in salivary gland carcinomas. Copyright

Autonomously Functioning Thyroid Nodule with Papillary Microcarcinoma and Lymph Node Metastasis: A Case Report

2.5×2cm in the right lobe and a nodule measuring 5×4.5cm in the left lobe. The left lobe nodule was hyperfunctioning on Tc-99m imaging. On the other hand, the right lobe nodule showed uptake on delayed T1-201 imaging and was suggested to be malignant. Fine needle aspiration biopsy using ultrasonography was class V (papillary carcinoma) for the right lobe nodule and class II for the left lobe nodule. The patient underwent total thyroidectomy and right regional neck dissection. Histopathological examination revealed two papillary microcarcinomas (each 5mm in diameter) surrounded by nodular hyperplasia in the right lobe, nodular hyperplasia in the left lobe, and right pretracheal and paratracheal lymph node metastasis. Since it is not rare for cancer to be associated with AFTN, care must be taken to obtain an accurate diagnosis in such cases and surgery is the treatment of choice for AFTN.

Temporal Bone Metastasis of Renal Cell Carcinoma. A Case Report.

Renal cell carcinomas rarely metastasize to the bones of the skull. We report here the case of a renal cell carcinoma that metastasized to the temporal bone.The patient was an 85-year-old female who had been diagnosed with renal cell carcinoma and had undergone a left nephrectomy in October 1987. In December 2000, she noticed a swelling in her left temporal region. The tumor was 35×50mm, elastic and soft, and accompanied with a heartbeat upon palpation. A blood-filled tumor which had destroyed the left temporal bone without penetrating into the dura mater, with metastasis to the right ribs, was detected by CT, MRI, US and cerebral angiography (radiological features). It was diagnosed as a metastatic renal cell carcinoma of the alveolar, common clear cell subtype by open biopsy. We judged that it was impossible to perform a curative resection, so the patient was treated internally with cimetidine which has an immunity activation action. It was also important to maintain her quality of life and to boost her immunity.Renal cell carcinomas tend to be highly metastatic, and metastasis after more than ten years is not uncommon. Therefore, it is prudent to always take renal cell carcinoma into consideration in the differential diagnosis of blood-filled tumors. In addition, caution should be exercised since these tumors are friable and tend to bleed during diagnosis and treatment.

The Utility and the Limitations of Ultrasonography for Lymph Node Metastases.

Ultrasonography (US) is a very useful examination tool to evaluate cervical lymph node swelling in cases of head and neck cancer. Many reports have demonstrated that US is more reliable than palpation, CT or MRI for evaluating lymph nodes. Cervical lymph nodes removed by radical neck dissection from 19 cases with head and neck carcinomas were examined histopathologically, and observations were compared with preoperative US findings. Metastatic lymph nodes were diagnosed by size on US. Lymph nodes exceeding 7mm in Level 1 and 6mm in other cervical regions were diagnosed as metastases. A total of 457 lymph nodes were removed by radical neck dissection and 58 lymph nodes were positive for metastasis histopathologically. Twenty-nine of 58 lymph nodes were determined to be positive for metastases by preoperative US and they were all positive in histopathological examinations after operation. Since it is often difficult to detect the number of positive lymph nodes by US, there is a high possibility of multiple metastatic lymph nodes when one metastatic lymph node is detected by US findings. The prognosis of head and neck carcinomas is thought to depend on the number of metastatic lymph nodes, therefore, radical neck dissection should be performed in cases of positive lymph nodes detected by US findings.