Kuniyuki Oka

Carbon beam therapy overcomes the radiation resistance of uterine cervical cancer originating from hypoxia.

Purpose: High linear energy transfer (LET) particles are believed to decrease tumor radiation resistance originating from hypoxia. However, no proof of this effect has been provided by clinical trials and related clinical research. Hence, we investigated the radiation biological aspects of high LET carbon beam therapy on cervical cancer. Experimental Design: This study involved 49 patients with stage IIIb bulky and stage IVa cervical cancer treated with high LET carbon beams between October 1995 and June 2000. Oxygen partial pressure (pO2) was measured by using a needle-type polarographic oxygen electrode. Results: The 4-year disease-free survival rates of patients with pO2 ≤ 20 mm Hg (hypoxic tumor) and pO2 > 20 mm Hg (oxygenated tumor) before treatment were 37% and 21%, respectively. The local control rates of hypoxic and oxygenated tumors before treatment were 58% and 54%, respectively. The disease-free survival rates of hypoxic and oxygenated tumors assessed by oxygen status at the 5th day of irradiation were 33% and 32%, respectively. The local control rates of hypoxic and oxygenated tumors at the 5th day were 60% and 58%, respectively. There was no significant prognostic difference between hypoxic and oxygenated tumors. Conclusion: The similar disease-free survival and local control rates between hypoxic and oxygenated tumors before and during treatment indicated that the role of the tumor oxygenation status was not so important in local control in carbon beam therapy. These results indicated that high LET carbon beam irradiation might reduce the radiation-resistant nature stemming from tumor hypoxia.

c-erbB-2 oncoprotein expression related to chemoradioresistance in esophageal squamous cell carcinoma

PURPOSE Esophageal carcinoma is a challenging target for radiotherapy. To improve treatment efficacy, an investigation of a predictive factor is desirable. In this study, we evaluated the significance of apoptosis and immunohistochemical staining for p53, Ki-67, c-erbB-2 (HER-2/neu), Ku (p70/p80), and DNA-PKcs for predictive markers of the responsiveness to chemoradiotherapy in esophageal squamous cell carcinoma. MATERIALS AND METHODS This retrospective analysis consisted of 34 patients with esophageal squamous cell carcinoma in whom tumor biopsy was performed before treatment. They were divided into chemoradiosensitive (n = 13) and chemoradioresistant (n = 21) groups according to the tumor response evaluated at a total radiation dose of 40 Gy. The biopsy samples were examined with immunohistochemical staining for various factors and with an in situ nick end labeling method for apoptosis. The examined data were compared between the two groups. RESULTS The difference in the Ki-67, p53, Ku (p70/p80), DNA-PKcs labeling indexes and the apoptosis index in tumor cells between the chemoradiosensitive and chemoradioresistant groups was not statistically significant. The expression of c-erbB-2 oncoprotein was statistically significant in the chemoradioresistant group (p = 0.02), although it did not correlate with survival. CONCLUSIONS c-erbB-2 immunostaining is useful for the prediction of chemoradioresistance in esophageal squamous cell carcinoma.

Correlation of cervical carcinoma c-erb B-2 oncogene with cell proliferation parameters in patients treated with radiation therapy for cervical carcinoma

Although c‐erb B‐2 oncoprotein expression (CerbB‐OPE) is believed to be associated with tumor cell proliferation and prognosis, the correlation between CerbB‐OPE and cell proliferation parameters has not been fully analyzed.

Benign clear cell tumor of the lung.

A 49-year-old woman presented with a solitary pulmonary nodule in the right lung. The tumor was well circumscribed and showed a reddish brown cut surface. It showed a diffuse growth pattern of polygonal cells with clear abundant cytoplasmand distinct cell border around thin-walled vascular spaces and sinusoid-type vessels. Based on morphological findings, the patient was diagnosed as having benign clear cell tumor of the lung. Silver impregnation and PAM stains showed fine reticular fibers continuously surrounding the vessels and individual neoplastic clear cells. Strong immunostaining for type IV collagen was observed surrounding all the individual clear cells. A few clear cells were positive for HMB-45 and NCAM 123C3 ( CD56 ). Electron microscopically, clear cells had numerous membrane-bound glycogen granules and a large amount of non—membrane-bound glycogen. The neoplastic cells were surrounded by external lamina and cytoplasmic processes. The neoplastic clear cells showed morphologic features seen in pericytes, melanocytic cells, and neuroendocrine cells.

Transition of ki‐67 index of uterine cervical tumors during radiation therapy. Immunohistochemical study

Histopathologic and Ki‐67‐staining features of cancer cells were investigated in biopsy specimens before and during radiation therapy in 29 patients with cervical squamous cell carcinoma. No morphologic changes were observed up to doses of 540 cGy. A few intact cancer cells remained up to doses of 2700 cGy. Moderate changes in the cancer cells were noticed in patients who received 900 cGy or more, i.e., multinuclei, swollen nuclei and cytoplasms, and prominent large nucleoli. At doses of 1800 cGy or greater, many cancer nests had severely damaged cancer cells with features such as cytolysis, karyolysis, karyorrhexis, pyknosis, and bizarre giant cells. There was no mitosis in the cells of patients who received doses greater than 1800 cGy. The Ki‐67‐positive cancer cells showed diffuse nuclear‐stainings and dot‐stainings before radiation therapy. Radiation doses more than 900 cGy changed the staining pattern of the Ki‐67 antibody; large irregular spot‐stainings and ring‐stainings were observed predominantly. The Ki‐67 index initially increased with the radiation dose; the mean Ki‐67 indices before radiation therapy and at radiation doses of 180 cGy, 540 cGy, and 900 cGy were 41%, 50%, 63%, and 68%, respectively. The indices decreased when the dose was increased further, and they were 39% and 20% at doses of 1800 cGy and 2700 cGy, respectively. Possible explanations, including recruitment of quiescent cells, for the change in Ki‐67 staining are discussed.

MIB1 growth fraction is not related to prognosis in cervical squamous cell carcinoma treated with radiotherapy.

A monoclonal antibody, MIB1, recognizes Ki-67 antigen in routinely processed paraffin sections after microwave treatment. Cycling cells are positive for MIB1, and quiescent cells are negative for MIB1. MIB1 index represents the growth fraction of the cell population. Cervical biopsies taken from 186 patients with stage III squamous cell carcinoma prior to radiotherapy were investigated for MIB1 reactivity using an immunohistochemical method. Cancer cells that were positive for MIB1 showed an intranuclear or chromosomal positive pattern. The median MIB1 index was 43% (range, 18-74%). Of 186 patients, 87 had a MIB1 index of > 43% and the other 99 had an index of < 43%. The 5-year survival rates were 58% (50 of 87 patients) in the former group and 58% (57 of 99 patients) in the latter group. The chi 2 test indicated that no significant prognostic correlation existed between two groups (p = 0.989). We conclude that the MIB1 index demonstrates a considerable variation among patients and is not a predictive indicator of survival for patients with stage III cervical squamous cell carcinoma.

Analysis of response to radiation therapy of patients with cervical adenocarcinoma compared with squamous cell carcinoma. MIB-1 and PC10 labeling indices.

The MIB‐1 monoclonal antibody is a marker of cycling cells and the PC10 monoclonal antibody is a marker of proliferating cell nuclear antigen in paraffin sections. This study was conducted to elucidate the difference in response to radiotherapy (RT) between cervical adenocarcinomas and squamous cell carcinomas, focusing on cell proliferation.

CEROID-LIKE HISTIOCYTIC GRANULOMA OF GALL-BLADDER — A PREVIOUSLY UNDESCRIBED LESION —

In the present study, 13 cases of a peculiar gall‐bladder granuloma characterized by marked proliferation of ceroid‐fllled brown histiocytes were pathomorphologically, histochemically and ultrastructurally examined to define the pathologic features of such a lesion previously undescribed in the literature. The lesion grossly showed a granulomatous appearance of yellow brown to dark brown color developing in the wall of gall‐bladder. Histologically, there was proliferation of histiocytes containing abundant brown pigment granules In their cytoplasm. The pigment granules proved to have staining characteristics closely resembling those of lipogenic ceroid‐like pigment. Ultrastructurally, these granules showed membrane‐bound, pleomorphic osmiophilic inclusions of heterogenous materials. With regard to the pathogenesis of this granuloma, it may be suggested that lipid components of bile juice, particularly unsaturated fatty acids and phospholipids, play an Important role as a source of ceroidogenesis In the proliferating histiocytes.

PD-ECGF POSITIVITY CORRELATES WITH BETTER SURVIVAL, WHILE iNOS HAS NO PREDICTIVE VALUE FOR CERVICAL CARCINOMAS TREATED WITH RADIOTHERAPY

PURPOSE Platelet-derived endothelial cell growth factor (PD-ECGF), which has angiogenic activity, is identical to thymidine phosphorylase. Tumor vascularization is considered to be an important prognostic factor. Nitric oxide synthases (NOSs) are a kind of enzyme that generates nitric oxide. Nitric oxide has not only a self defense against neoplastic cells but also tumor growth stimulation by promoting new blood vessel formation. Our purpose was to investigate the correlation between the expression of PD-ECGF or inducible NOS (iNOS) in cancer cells and prognosis. METHODS AND MATERIALS Formaldehyde-fixed and paraffin-embedded biopsy specimens excised from 71 cervical squamous cell carcinoma patients who were treated with radiotherapy alone were investigated using an immunohistochemical method. RESULTS Cancer cells that were positive for PD-ECGF showed intranuclear and cytoplasmic staining patterns. Of the 71 patients, 40 (56%) were positive for PD-ECGF and 31 (44%) were negative. The 5-year survival of the PD-ECGF-positive patients was significantly better than that of the PD-ECGF-negative patients (p = 0.026). Cancer cells that were positive for iNOS showed a cytoplasmic staining pattern. Twenty-seven patients (38%) were positive for iNOS and 44 (62%) were negative. No significant prognostic correlation was observed between iNOS-positive and iNOS-negative patients. CONCLUSION PD-ECGF positivity in cancer cells is a predictive factor for a good prognosis in cervical squamous cell carcinoma treated with radiotherapy alone.

Chordoid meningioma. A Case Report

We report on a 62-year-old woman without Castlemans syndrome diagnosed with chordoid meningioma. A white, encapsulated brain tumor was located in the parietal lobe of the left hemisphere of the cerebrum, adhered to the dura, and was separated from the cerebrum. The tumor revealed a multilobular arrangement of two types of neoplastic cells, and the surrounding myxoid stroma was separated by incomplete fibrous septa. Neoplastic cells consisted of myxomatous and meningothelial cells. The former made up about four-fifths of the tumor, had a vacuolar cytoplasm, and were arranged in a chordoma-like cord pattern. They were floating in myxoid stroma. The latter had an eosinophilic spindle or epithelioid cytoplasm and were disposed in lobules. Coarse eosinophilic materials positive for periodic acid-Schiff stain were deposited among them. Transitional cells between two types of cells were also observed. Both neoplastic cells were positive for vimentin and Leu-7 (CD57) in their cytoplasm, and were consistently negative for epithelial membrane antigen, S-100 protein, and cytokeratin.