Woo-Sung Moon

Reduced expression of epidermal growth factor receptor related protein in gastric cancer

Objectives: The recently cloned epidermal growth factor receptor related protein (ERRP) has been proposed to be a negative regulator of the epidermal growth factor receptor (EGFR). Because of the causal involvement of EGFR and its ligands in gastric cancer growth, we investigated expression of ERRP and cell proliferation in human gastric cancer. Methods: We examined ERRP expression and localisation in surgical specimens of gastric cancers from 47 patients versus non-malignant gastric mucosa and determined their relationship to cell proliferation and differentiation. We also examined expression of ERRP by western blotting in three different gastric cancer cell lines. To further determine the functional properties of ERRP, we examined the effect of ERRP on epidermal growth factor (EGF) induced EGFR phosphorylation essential for its activation in MKN-28 gastric cancer cells. Results: ERRP expression was dramatically reduced in gastric cancers (34% of all specimens positive) compared with non-malignant gastric mucosa (66% of specimens positive). Expression of ERRP in cancer cells inversely correlated with cell proliferation and grade of malignancy. Cell lines derived from metastatic gastric cancers had reduced ERRP expression compared with cell lines derived from a non-metastatic cancer. Exogenous ERRP protein markedly inhibited EGF induced EGFR phosphorylation in gastric cancer cells providing a novel molecular mechanism of its action. Conclusions: Our data indicate that downregulation of ERRP could play an important role in gastric cancer differentiation and progression. ERRP is a negative regulator of tumour cell proliferation and may exert its inhibitory effect, in part, by attenuating EGFR activation.

A case of persistent endometriosis after total hysterectomy with both salpingo-oophorectomy managed by radiation therapy.

Abstractu2002Persistent endometriosis after total hysterectomy and both salpingo-oophorectomy (TH with BSO) is a rare condition and the etiology is uncertain. The exact incidence of persistent endometriosis after definitive surgery is not known. In addition, the treatment of persistent endometriosis after complete surgical excision is controversial. We report a case of persistent endometriosis with vaginal and sigmoid-colonic invasion after TH with BSO. The lesions were not responsive to hormonal therapy. The patient was managed successfully by therapeutic pelvic radiation.

Bizarre leiomyoma of the soft tissue

Sir, Bizarre leiomyoma of soft tissue has been previously described rarely. There have been only two cases of bizarre leiomyoma reported in the nasal cavity but none at all in the nasolabial fold, although a few cases of leiomyoma have been reported in the nasal cavity and paranasal sinuses. A 34-year-old man had been suffering from a mass in the nasolabial fold for 1 year. The patient had an unremarkable clinical history, except for untreated hypertension and flank pain. On examination, a soft, indolent, and movable mass was observed on the left nasolabial fold. Rhinoscopic examination displayed mild septal deviation on the right side, and elevation of the nasal floor. Under the clinical impression of a nasolabial cyst, the mass was completely excised by sublabial approach. Grossly, the specimen consisted of a 30622620 mm solid mass. The mass exhibited soft yellow colouration with haemorrhaging on the cut surface. Microscopically, the lesion was well circumscribed, and revealed overall hypercellularity, excepting the haemorrhagic and focal loose stromal areas (Fig. 1). There were small-sized, thinwalled vessels, but no thick-walled vessels in hypercellular areas. The hypercellular area, composed of spindle cells and bizarre cells, formed vague nodules and intersecting fascicles. The spindle cells had deeply eosinophilic cytoplasm and blunt-ended nuclei. The bizarre cells, distributed diffusely throughout the tumour, had pleomorphic features such as epithelioid cells, mononucleated or multinucleated giant cells, and bizarre cells with smudged chromatin. Inflammatory cells were scattered between the tumour cells and clustered in the perivascular area. Mitoses including atypical figures and tumour cell necrosis were not found. Immunohistochemically, the tumour cells stained strongly for smooth muscle actin (SMA) and vimentin, but negatively for Ki-67, p53, cytokeratin, CD34, desmin, S100 protein, HMB45, and myoglobin. The patient has demonstrated no evidence of recurrence or metastasis over a period of 30 months. These immunohistochemical findings, in combination with the absence of mitosis and tumour cell necrosis, the indolent clinical course, and the lack of an infiltrative growth pattern, led to the diagnosis of bizarre leiomyoma. Enzinger and Weiss considered pronounced nuclear pleomorphism to be a kind of degenerative aspect in a long standing lesion. Novak and Anderson referred to multinucleated giant cells with pleomorphic nuclei as those of symplastic type and also concluded that they resulted from degeneration. The vascular alterations of fibrinoid change, inflammation, and the thrombi, unusual findings in leiomyoma, may be important in the genesis of bizarre leiomyoma. Downes and Hart presented a study of 24 bizarre uterine leiomyomas, which came to exactly that conclusion. In approaching our case, our main difficulty was in defining malignant potential. In soft tissue, Billings et al. suggest that tumours with less than 1 mitosis per 50 high power fields (HPF) can be classified as leiomyoma, while tumours with a low mitotic rate (1 to 5 mitoses per 50 HPF) may be considered to be of uncertain malignant potential. However, there may be quite a bit of difficulty in estimation of mitotic rate in bizarre leiomyomas because the details of nuclear contour are modified by degeneration. Yavuz et al. concluded that, in addition to conventional criteria, both the Ki-67 immunostaining index and mast cell count can be used as adjunct findings in the differential diagnosis between leiomyosarcoma and atypical leiomyoma. Thick-walled vessels, an important component of angiomyoma, were not recognised in our case. In addition, we performed reticulin stains to highlight vascular elements, and only small-sized, thin-walled vessels were identified. Malignant melanoma could be excluded by the absence of prominent nucleoli and high mitotic rates, and the negative staining for S100 protein. The lack of high mitotic activity and the negative immunostaining for cytokeratin excluded a sarcomatoid carcinoma. Myofibroblastic tumours mainly consist of spindle cells with a paler and less fibrillary cytoplasm than that of smooth muscle cells. In addition, the myofibroblastic tumour cells do not stain uniformly for SMA, as is often seen in leiomyogenic tumours. In summary, we have discussed the morphological features and differential diagnosis of a case of bizarre leiomyoma of the nasolabial fold. The prognosis and histogenesis of bizarre leiomyoma of the soft tissue remain to be determined by the accumulation of additional cases.