PATHOLOGY DIVISION

19.PATHOLOGY DIVISION

    The research activities of the Pathology Division of the Research Institute East currently concentrate on applying morphological study of cancer tissue to clinical diagnosis and treatment. Prognostic factors and other 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 Implications

    Cancer-stromal interaction plays important roles in not only carcinogenesis but also cancer progression, including invasion and metastasis.⁽¹⁹⁶⁾ Cancer stroma consists of various types of cells including endothelial cells constituting blood vessels, lymph vessels, fibroblasts and inflammatory cells containing macrophages and lymphocytes. Mitotic figures of fibroblasts are seen within invasive ductal carcinoma (IDC) of the breast and the metastatic ability of IDCs was found to be highly dependent on the proliferative activity of fibroblasts in the inner area. This suggests that the proliferative activity of fibroblasts may play an important role in IDC tumor progression. IDCs of the breast with a fibrotic focus also demonstrated more frequent bone metastasis.^(197,¹⁹⁸⁾
    In addition to the roles of cancer stroma in cancer development, the power of tumor thickness of Dukes stage C colorectal cancer was estimated for predicting metachronous liver metastasis, lymph node metastasis, and overall survival. The thickness of the central depressed area of colorectal cancers was found to be a useful predictive parameter for metachronous liver metastasis, multiple lymphnode metastasis, and overall survival in colorectal cancer patients.⁽¹⁹⁹⁾
Clinicopathological Study of Atypical Adenomatous Hyperplasia (AAH) as a Precancerous Lesion of Lung Adenocarcinoma

    Although atypical adenomatous hyperplasia (AAH) has been regarded as a precursor of lung adenocarcinoma because of histological similarity in their growth patterns, there is no clinicopathlogical evidence supporting this assumption. The characteristics of AAH were clarified in the general elderly population on the basis of autopsy findings and AAH was found to be more common in cases with than in those without malignancy.⁽²⁰⁰⁾ A low incidence of lung carcinoma has been reported in cases of prolonged aspirin use. Cyclooxygenase (COX)2 expression is frequently seen in adenocarcinoma of the lung, but COX-2 expression in AAH is not known. COX-2 expression was immunohistochemically evaluated in cuboidal cell hyperplasias, AAH, bronchioloalveolar carcinomas (BAC), and invasive adenocarcinomas. COX-2 overexpression was frequently found in both AAH and BAC. No relationship was found between COX-2 expression and clinicopathological factors or survival. These findings, considered with previous reports that treatment with a COX-2 inhibitor suppresses human colon carcinogenesis, suggest that inhibition of COX-2 may reduce the incidence of human adenocarcinoma of the lung.⁽²⁰¹⁾
Evaluation of Histopathological Factors in the Treatment of Cancer

    In order to confirm the histopathological criteria for minimally invasive adenocarcinoma of the lung, 200 cases of adenocarcinoma of the lung were examined clinicopathologically. Both favorable and unfavorable morphological prognostic factors were defined by statistical analysis. Vascular invasion and a greater than 25% papillary growth component were the most significant determinants of an unfavorable outcome. The favorable and unfavorable factors demonstrated in this study will be of great value in determining whether minimally invasive adenocarcinoma of the lung can be treated with limited surgery.^(202,²⁰³⁾
    In order to assess clinicopathological factors for evaluating the effectiveness of 5-FU based therapy, the relationship between TS and DPD expression and the effects of chemotherapy were investigated using biopsy specimens of advanced gastric cancer with S-1 therapy. However, there was no significant difference in median survival time between TS(+) patients and TS(-) patients. This study indicates that S-1 may be effective in the treatment of gastric cancer patients, regardless of intratumoral TS and DPD immunoreactivity status.
    The relations between radiosensitivity and clinicopathological factors were investigated in biopsy specimens from laryngeal squamous cell carcinoma (LSCC) patients given radiotherapy. Univariate and multivariate analyses showed that microvessel density (MVD) alone had significant predictive power for radiosensitivity in T1 and T2 stage LSCCs after radiotherapy and that MVD is a potentially useful clinical factor predicting radiosensitivity.⁽²⁰⁴⁾
Clinicopathological Studies on Various Cancers

    A rare case with lung,^(205-²⁰⁸⁾ and liver⁽²⁰⁹⁾ cancer was reported. Other clinicopathological studies were also conducted to enhance the diagnosis and treatment of tumors.^(210,²¹¹⁾




19.PATHOLOGY DIVISION



	The research activities of the Pathology Division of the Research Institute East currently concentrate on applying morphological study of cancer tissue to clinical diagnosis and treatment. Prognostic factors and other 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 Implications Cancer-stromal interaction plays important roles in not only carcinogenesis but also cancer progression, including invasion and metastasis.⁽¹⁹⁶⁾ Cancer stroma consists of various types of cells including endothelial cells constituting blood vessels, lymph vessels, fibroblasts and inflammatory cells containing macrophages and lymphocytes. Mitotic figures of fibroblasts are seen within invasive ductal carcinoma (IDC) of the breast and the metastatic ability of IDCs was found to be highly dependent on the proliferative activity of fibroblasts in the inner area. This suggests that the proliferative activity of fibroblasts may play an important role in IDC tumor progression. IDCs of the breast with a fibrotic focus also demonstrated more frequent bone metastasis.^(197,¹⁹⁸⁾ In addition to the roles of cancer stroma in cancer development, the power of tumor thickness of Dukes stage C colorectal cancer was estimated for predicting metachronous liver metastasis, lymph node metastasis, and overall survival. The thickness of the central depressed area of colorectal cancers was found to be a useful predictive parameter for metachronous liver metastasis, multiple lymphnode metastasis, and overall survival in colorectal cancer patients.⁽¹⁹⁹⁾ Clinicopathological Study of Atypical Adenomatous Hyperplasia (AAH) as a Precancerous Lesion of Lung Adenocarcinoma Although atypical adenomatous hyperplasia (AAH) has been regarded as a precursor of lung adenocarcinoma because of histological similarity in their growth patterns, there is no clinicopathlogical evidence supporting this assumption. The characteristics of AAH were clarified in the general elderly population on the basis of autopsy findings and AAH was found to be more common in cases with than in those without malignancy.⁽²⁰⁰⁾ A low incidence of lung carcinoma has been reported in cases of prolonged aspirin use. Cyclooxygenase (COX)2 expression is frequently seen in adenocarcinoma of the lung, but COX-2 expression in AAH is not known. COX-2 expression was immunohistochemically evaluated in cuboidal cell hyperplasias, AAH, bronchioloalveolar carcinomas (BAC), and invasive adenocarcinomas. COX-2 overexpression was frequently found in both AAH and BAC. No relationship was found between COX-2 expression and clinicopathological factors or survival. These findings, considered with previous reports that treatment with a COX-2 inhibitor suppresses human colon carcinogenesis, suggest that inhibition of COX-2 may reduce the incidence of human adenocarcinoma of the lung.⁽²⁰¹⁾ Evaluation of Histopathological Factors in the Treatment of Cancer In order to confirm the histopathological criteria for minimally invasive adenocarcinoma of the lung, 200 cases of adenocarcinoma of the lung were examined clinicopathologically. Both favorable and unfavorable morphological prognostic factors were defined by statistical analysis. Vascular invasion and a greater than 25% papillary growth component were the most significant determinants of an unfavorable outcome. The favorable and unfavorable factors demonstrated in this study will be of great value in determining whether minimally invasive adenocarcinoma of the lung can be treated with limited surgery.^(202,²⁰³⁾ In order to assess clinicopathological factors for evaluating the effectiveness of 5-FU based therapy, the relationship between TS and DPD expression and the effects of chemotherapy were investigated using biopsy specimens of advanced gastric cancer with S-1 therapy. However, there was no significant difference in median survival time between TS(+) patients and TS(-) patients. This study indicates that S-1 may be effective in the treatment of gastric cancer patients, regardless of intratumoral TS and DPD immunoreactivity status. The relations between radiosensitivity and clinicopathological factors were investigated in biopsy specimens from laryngeal squamous cell carcinoma (LSCC) patients given radiotherapy. Univariate and multivariate analyses showed that microvessel density (MVD) alone had significant predictive power for radiosensitivity in T1 and T2 stage LSCCs after radiotherapy and that MVD is a potentially useful clinical factor predicting radiosensitivity.⁽²⁰⁴⁾ Clinicopathological Studies on Various Cancers A rare case with lung,^(205-²⁰⁸⁾ and liver⁽²⁰⁹⁾ cancer was reported. Other clinicopathological studies were also conducted to enhance the diagnosis and treatment of tumors.^(210,²¹¹⁾