PATHOLOGY DIVISION

21.PATHOLOGY DIVISION

    The research activities of the Pathology Division of the Research Institute East currently concentrate on the application of the morphological study of cancer tissue to clinical diagnosis and treatment. Prognostic factors and clinicopathological characteristics of various cancers have been studied in collaboration with clinical departments of the National Cancer Center Hospital East.
Cancer-Stromal Interaction and Its Clinical Implication

    Cancer-stromal interaction plays important roles in not only carcinogenesis but also cancer progression such as invasion and metastasis. Macroscopic typing with structure signs that are related to the quantity of fibrosis, reflects tumor aggressiveness of advanced colorectal cancer.⁽²²⁰⁾ Mitotic figures of fibroblasts and a high microvessel index are seen and vary within colorectal cancers, and we found that the metastatic ability of the T3 ulcerative-type colorectal cancer is closely dependent on the proliferative activity of fibroblasts and the upper area of the central depressed area in the ulcerative-type colorectal cancer.⁽²²¹⁾ This is also observed in the high proliferative activity of fibroblasts in invasive ductal carcinoma of the breast.⁽²²²⁾ The morphological characteristic of bone metastasis of prostate cancer is its osteoplasia. In order to investigate the mechanisms for osteoplastic bone metastasis of prostatic cancer, an animal model for bone metastasis of human prostatic cancer cells to human bone was established using NOD-SCID mice.⁽²²⁴⁾
Evaluation of Histopathological Factors on the Treatment for Cancer.

    The relations between radiosensitivity and clinicopathological factors were investigated in biopsy specimens from laryngeal squamous cell carcinoma (LSCC) patients given radiotherapy and found that the microvessel density (MVD) alone had significant predictive power for radiosensitivity in early stage LSCCs after radiotherapy. Furthermore, MVD was seemed to be a potentially useful clinical factor for predicting radiosensitivity.⁽²²⁵⁾ In addition to LSCC, the radiosensitivity of metastatic head and neck squamous cell carcinoma in the cervical lymph nodes has been investigated and it was found that high grade keratinization and low MVD were significantly associated with radioresistance.⁽²²⁶⁾ These studies indicate that the tissue oxygen level calculated from MVD is most significant factor related to radiosensitivity that has been reported. In order to assess clinicopathological factors for evaluating the effectiveness of 5-FU based therapy, the relationship among TS, DPD expression and their kinase activity were investigated using surgical specimens of colon cancer. However, there was no difference among expression and kinase activity.⁽²²⁰⁾
Multistep Carcinogenesis of Lung Adenocarcinoma.

    Lung cancer is the leading cause of death in Japan. Unlike squamous cell carcinoma, the multistep carcinogenesis of lung adenocarcinoma has not been elucidated yet. Accumulation of losses of heterozygosity was investigated in 66 cases of lung adenocarcinomas and it was found that the LOH rate increased in the course from localized bronchioloalveolar carcinoma (LBAC), LBAC with alveolar collapse to LBAC with active fibroblastic proliferation.⁽²²⁷⁾ In order to elucidate lung carcinogenesis, clinicopathological studies on lung cancer have been performed in cases with idiopathic pulmonary fibrosis⁽²²⁸⁾ and occupational lung cancers.⁽²²⁹⁾ The characteristics of atypical adenomatous hyperplasia (AAH) were clarified in the basis of the findings in autopsy cases and it was found that AAH was more common in the cases with malignancy than in those without.⁽²³⁰⁾ Clinicopathological studies on 508 consecutive primary lung cancer patients were also performed and showed that AAH lesions were significantly associated with adenocarcinoma of the lung, especially with multiple primary adenocarcinoma.⁽²³¹⁾
Clinicopathological Studies on Various Cancers

    Rare cases of esophagus,^(222,²²³⁾ stomach,⁽²³²⁾ liver⁽²³³⁾ and lung⁽²³⁴⁾ cancer have been reported. Other clinicopathological studies were also conducted to promote the diagnosis and treatment of tumors.^(235-²³⁷⁾




21.PATHOLOGY DIVISION



	The research activities of the Pathology Division of the Research Institute East currently concentrate on the application of the morphological study of cancer tissue to clinical diagnosis and treatment. Prognostic factors and clinicopathological characteristics of various cancers have been studied in collaboration with clinical departments of the National Cancer Center Hospital East. Cancer-Stromal Interaction and Its Clinical Implication Cancer-stromal interaction plays important roles in not only carcinogenesis but also cancer progression such as invasion and metastasis. Macroscopic typing with structure signs that are related to the quantity of fibrosis, reflects tumor aggressiveness of advanced colorectal cancer.⁽²²⁰⁾ Mitotic figures of fibroblasts and a high microvessel index are seen and vary within colorectal cancers, and we found that the metastatic ability of the T3 ulcerative-type colorectal cancer is closely dependent on the proliferative activity of fibroblasts and the upper area of the central depressed area in the ulcerative-type colorectal cancer.⁽²²¹⁾ This is also observed in the high proliferative activity of fibroblasts in invasive ductal carcinoma of the breast.⁽²²²⁾ The morphological characteristic of bone metastasis of prostate cancer is its osteoplasia. In order to investigate the mechanisms for osteoplastic bone metastasis of prostatic cancer, an animal model for bone metastasis of human prostatic cancer cells to human bone was established using NOD-SCID mice.⁽²²⁴⁾ Evaluation of Histopathological Factors on the Treatment for Cancer. The relations between radiosensitivity and clinicopathological factors were investigated in biopsy specimens from laryngeal squamous cell carcinoma (LSCC) patients given radiotherapy and found that the microvessel density (MVD) alone had significant predictive power for radiosensitivity in early stage LSCCs after radiotherapy. Furthermore, MVD was seemed to be a potentially useful clinical factor for predicting radiosensitivity.⁽²²⁵⁾ In addition to LSCC, the radiosensitivity of metastatic head and neck squamous cell carcinoma in the cervical lymph nodes has been investigated and it was found that high grade keratinization and low MVD were significantly associated with radioresistance.⁽²²⁶⁾ These studies indicate that the tissue oxygen level calculated from MVD is most significant factor related to radiosensitivity that has been reported. In order to assess clinicopathological factors for evaluating the effectiveness of 5-FU based therapy, the relationship among TS, DPD expression and their kinase activity were investigated using surgical specimens of colon cancer. However, there was no difference among expression and kinase activity.⁽²²⁰⁾ Multistep Carcinogenesis of Lung Adenocarcinoma. Lung cancer is the leading cause of death in Japan. Unlike squamous cell carcinoma, the multistep carcinogenesis of lung adenocarcinoma has not been elucidated yet. Accumulation of losses of heterozygosity was investigated in 66 cases of lung adenocarcinomas and it was found that the LOH rate increased in the course from localized bronchioloalveolar carcinoma (LBAC), LBAC with alveolar collapse to LBAC with active fibroblastic proliferation.⁽²²⁷⁾ In order to elucidate lung carcinogenesis, clinicopathological studies on lung cancer have been performed in cases with idiopathic pulmonary fibrosis⁽²²⁸⁾ and occupational lung cancers.⁽²²⁹⁾ The characteristics of atypical adenomatous hyperplasia (AAH) were clarified in the basis of the findings in autopsy cases and it was found that AAH was more common in the cases with malignancy than in those without.⁽²³⁰⁾ Clinicopathological studies on 508 consecutive primary lung cancer patients were also performed and showed that AAH lesions were significantly associated with adenocarcinoma of the lung, especially with multiple primary adenocarcinoma.⁽²³¹⁾ Clinicopathological Studies on Various Cancers Rare cases of esophagus,^(222,²²³⁾ stomach,⁽²³²⁾ liver⁽²³³⁾ and lung⁽²³⁴⁾ cancer have been reported. Other clinicopathological studies were also conducted to promote the diagnosis and treatment of tumors.^(235-²³⁷⁾