PubMed Health⌕ Search

Biomedical subjects

Masayuki Noguchi

Publications and source records attributed to Masayuki Noguchi.

At least 19 recordsLinked to original sources

OCIA domain containing 2 is highly expressed in adenocarcinoma mixed subtype with bronchioloalveolar carcinoma component and is associated with better prognosis.

Although lung adenocarcinoma is a major cause of cancer death worldwide, details of its molecular carcinogenesis and stepwise progression are still unclear. To characterize the sequential progression from bronchioloalveolar adenocarcinoma of the lung (BAC, in situ carcinoma) to adenocarcinoma mixed subtype with BAC component polymerase chain reaction-based cDNA suppression subtractive hybridization (SSH) was carried out using two representative cases of BAC (non-invasive tumors) and adenocarcinoma mixed subtype with BAC (invasive tumors). Through differential screening, virtual reverse northern hybridization and quantitative real-time reverse-transcription-polymerase chain reaction (qRT-PCR) we selected five genes (TncRNA, OCIAD2, ANXA2, TMED4 and LGALS4) that were expressed at significantly higher levels in invasive adenocarcinoma mixed subtype with BAC than in BAC. After in situ hybridization and qRT-PCR analyses, we confirmed that only the OCIAD2 gene showed significantly higher expression in the tumor cells of invasive adenocarcinoma mixed subtype with BAC than in BAC (P = 0.026). We then carried out in situ hybridization of OCIAD2 in 56 adenocarcinoma mixed subtype with BAC component and assessed the correlation between OCIAD2 expression and clinicopathological features. In contrast to our expectation, the patients with OCIAD2 expression showed a better clinical outcome than those without OCIAD2 expression, and OCIAD2 expression showed an inverse correlation with lymphatic invasion, blood vessel invasion and lymph node metastasis. These results suggest that OCIAD2 begins to express at the progression from in situ to invasive carcinoma, and is associated with the favorable prognosis of adenocarcinoma mixed subtype with BAC component.

Adenocarcinoma↗

Consistent liver metastases in a rat model by portal injection of microencapsulated cancer cells.

Consistent liver metastases in animal models is generally observed only with certain cancer cell lines. With the aim of improving on existing animal models of liver metastases, we hypothesized that cancer cells encased in 300 microm microcapsules, mimicking micrometastatic foci, might be effective seeds of liver metastases. A total of 3,000 microcapsules, containing 700 to 1,500 viable cells/capsule in logarithmic growth phase of three human pancreatic cancer cell lines (SUIT-2, AsPC-1, and BxPC-3), were transplanted in nude rats by portal injection. The rate of liver metastases was 100% (12 of 12), 100% (6 of 6), and 83% (5 of 6) for SUIT-2, AsPC-1, and BxPC-3 microcapsules, respectively. In contrast, the administration of an identical number of single cancer cells (2.1-4.5 x 10(6)) did not lead to liver metastases. Metastases was strictly limited to the liver, was quite stable, and could be proportionately tailored by varying the number of cancer microcapsules administered. Microscopic observation showed that two-thirds of the cancer microcapsules were lodged in the peripheral small (20-50 microm) portal veins, although one-third of the cancer microcapsules were trapped in the central wide (200-400 microm) portal vein. Capsules began to burst at day 3, with recognizable metastases produced at day 7, resulting in overt metastases production at days 28 to 42. The present cancer microcapsule method may be useful for obtaining liver metastases in animal models, especially for cell lines that will not form liver metastases with conventional single cell injection methods and/or for experiments requiring the consistent formation of liver metastases.

Animals↗

Synchronous unilateral parotid gland neoplasms of three different histological types.

A 67-year-old male with three synchronous tumors in the unilateral parotid gland is reported. Postoperative histological examinations confirmed the presence of three synchronous primary tumors, specifically pleomorphic adenoma, Warthin's tumor and salivary duct carcinoma, in the right parotid gland. To our knowledge, this is the first case report describing three different histological types in the unilateral parotid gland.

Adenolymphoma↗

Identification of nerve growth factor-responsive element of the TCL1 promoter as a novel negative regulatory element.

The serine/threonine kinase, Akt (protein kinase B) plays a central role in the regulation of intracellular cell survival. Recently, we demonstrated that the proto-oncogene TCL1, overexpressed in human T-cell prolymphocytic leukemia, is an Akt kinase co-activator. Tightly restricted TCL1 gene expression in early developmental cells suggested that the TCL1 gene is regulated at a transcriptional level. To characterize how TCL1 gene expression is regulated, we cloned the 5'-promoter of the TCL1 gene located at human chromosome 14q32. The 5'-TCL1 promoter region contains a TATA box with cis-regulatory elements for Nur77/NGFI-B (nerve growth factor-responsive element (NBRE), CCAAGGTCA), NFkappaB, and fork head transcription factor. Nur77/NGFI-B, an orphan receptor superfamily transcription factor implicated in T-cell apoptosis, is a substrate for Akt. We hypothesized that TCL1 transactivity is regulated through Akt-induced phosphorylation of Nur77/NGFI-B in vivo. In an electrophoretic mobility shift assay with chromosomal immunoprecipitation assays, wild-type Nur77, but not S350A mutant Nur77, could specifically bind to TCL1-NBRE. A luciferase assay demonstrated that TCL1-NBRE is required for inhibition of TCL1 transactivity upon nerve growth factor/platelet-derived growth factor stimulation, which activates Akt and phosphorylates Nur77. Using a chromosomal immunoprecipitation assay with reverse transcription-PCR, nerve growth factor stimulation inhibited binding of endogenous Nur77 to TCL1-NBRE, in turn, suppressing TCL1 gene expression. The results together establish that TCL1-NBRE is a novel negative regulatory element of Nur77 (NGFI-B). To the best of our knowledge, TCL1-NBRE is the first direct target of Nur77 involving the regulation of intracellular cell death survival. This Akt-induced inhibitory mechanism of TCL1 should play an important role in immunological and/or neuronal development in vivo.

Animals↗

Immunohistochemical expression of mismatch repair genes: a screening tool for predicting mutator phenotype in liver fluke infection-associated intrahepatic cholangiocarcinoma.

AIM: To clarify possible contributions of DNA mismatch repair (MMR) system in carcinogenesis of liver fluke infection-associated intrahepatic cholangiocarcinoma (ICC) by using immunohistochemical assay. METHODS: A total of 29 ICC samples, which had been assessed for genomic instability by a PCR-based method, were used for study. They were examined immunohistochemically to demonstrate protein expression of two MMR genes, hMSH2 and hMLH1. Results obtained were compared with their mutator phenotype assessed previously. RESULTS: Either hMSH2 or hMLH1 protein was obviously expressed in 28 of 29 (96.6%) ICC samples. Positive nuclear localization of hMSH2 or hMLH1 protein was observed in 86.2% (25/29) or 93.1% (27/29) ICC cases, respectively, while their negative nuclear reactivity was only detected in 13.8% (4/29) or 6.9% (2/29) ICC cases analyzed, respectively. CONCLUSION: Our study, probably for the first time, showed through immunohistochemical detection of hMSH2 and hMLH1 gene that DNA MMR system does not play a prominent role in liver fluke infection-associated cholangiocarcinogenesis. These results confirm previous findings on mutational status of these genes assessed through a PCR-based method. The immunohistochemical analysis has proven to be an effective and sensitive approach for screening MMR deficiency regardless of somatic inactivation or promoter hypermethylation of hMSH2 and/or hMLH1 gene. Furthermore, immunohistochemistry is more advantageous compared to mutator phenotyping assay in terms of simplicity, less time consuming and cost effectiveness for screening possible involvements of target MMR genes in tumorigenesis.

Adaptor Proteins, Signal Transducing↗

Frequent EGFR mutations in noninvasive bronchioloalveolar carcinoma.

Mutations of the epidermal growth factor receptor gene (EGFR) have been reported to be present in a considerable fraction of lung adenocarcinomas showing dramatic response to EGFR tyrosine kinase inhibitors. To clarify pathogenic significance of the mutations for the development of lung adenocarcinoma, we investigated stage I lung adenocarcinomas for the mutations. First, 107 cases of macrodissected stage I adenocarcinomas were examined for mutations in exons 18-21 of the EGFR gene. EGFR mutations were detected in 36 of the 107 cases (34%). In particular, among the stage I cases, the mutations were detected in 17 of 42 small-sized adenocarcinomas (<or=2 cm in diameter) (40%), including 7 of 11 noninvasive bronchioloalveolar carcinomas (BACs) (64%) and 7 of 25 invasive adenocarcinomas with BAC components (28%). Second, 26 cases of laser capture microdissected small-sized adenocarcinomas, including 9 cases in the first analysis, were examined for the mutations. Reanalysis of microdissected materials in the 9 cases identified the mutations in 2 more adenocarcinomas with BAC components. Moreover, in the analysis of the other 17 microdissected materials, EGFR mutations were detected in 7 of 12 BACs (58%) and in 3 of 5 adenocarcinomas with BAC components (60%). EGFR mutations are present frequently in BACs, and are thus likely to be a critical genetic alteration for the formation of noninvasive lung adenocarcinoma.

Adenocarcinoma↗

CT-guided needle biopsy of lung lesions: a survey of severe complication based on 9783 biopsies in Japan.

PURPOSE: The aim of our study was to update the rate of severe complications following CT-guided needle biopsy in Japan via a mailed survey. MATERIALS AND METHODS: Postal questionnaires regarding CT-guided needle biopsy were sent out to multiple hospitals in Japan. The questions regarded: the total number and duration of CT-guided lung biopsies performed at each hospital, and the complication rates and numbers of pneumothorax, hemothorax, air embolism, tumor seeding, tension pneumothorax and other rare complications. Each severe complication was followed with additional questions. RESULTS: Data from 9783 biopsies was collected from 124 centers. Pneumothorax was the most common complication, and occurred in 2412 (35%) of 6881 cases. A total of 39 (35%) hospitals reported 74 (0.75%) cases with severe complications. There were six cases (0.061%) with air embolism, six cases (0.061%) with tumor seeding at the site of the biopsy route, 10 cases (0.10%) with tension pneumothorax, six cases (0.061%) with severe pulmonary hemorrhage or hemoptysis, nine cases (0.092%) with hemothorax, and 27 cases (0.26%) with others, including heart arrest, shock, and respiratory arrest. From a total of 62 patients with severe complications, 54 patients (0.55%) recovered without sequela, however one patient (0.01%) recovered with hemiplegia due to cerebral infarction, and the remaining seven patients (0.07%) died. CONCLUSIONS: This is the first national study documenting severe complications with respect to CT-guided needle biopsy in Japan. The complication rate in Japan is comparable to internationally published figures. We believe this data will improve both clinicians as well as patients understanding of the risk versus benefit of CT-guided needle biopsy, resulting better decisions.

Biopsy, Needle↗

Expression of the Bax inhibitor-1 gene in pulmonary adenocarcinoma.

BACKGROUND: The regulation of programmed cell death, or apoptosis, is crucial for normal development and for the maintenance of homeostasis. It has been shown that the novel antiapoptotic protein Bax inhibitor-1 (BI-1) represents a new type of regulator of cell death pathways controlled by Bcl-2 and Bax. METHODS: Surgically resected lung specimens were obtained from 32 patients with peripheral adenocarcinomas, and BI-1 gene expression was examined and compared with expression of the p53, bcl-2 and Bax genes. RESULTS: Fourteen of 32 tumors (43.8%) were positive for BI-1 gene expression by in situ hybridization. BI-1 gene expression in tumor specimens was significantly higher in adenocarcinomas with bronchioloalveolar carcinoma (BAC) and in adenocarcinomas of mixed subtypes with bronchioloalveolar spreading (14 of 17 tumors; 82.4%) than in carcinomas without it spreading. Patients who had BI-1-positive adenocarcinoma showed a relatively favorable prognosis compared with patients who had BI-1-negative adenocarcinoma. Eleven of 32 tumors (34.4%) were positive for the p53 protein, only 1 of 32 tumors (3.1%) was positive for the Bcl-2 protein, and 26 of 32 tumors (81.3%) were positive for the Bax protein. Protein expressions of p53, Bcl-2, and Bax, as detected by immunohistochemistry, were not associated with BI-1 gene expression. CONCLUSIONS: BI-1 gene expression was restricted to tumor cells with lepidic growth and was a prognostic factor for peripheral-type adenocarcinoma. It is believed that BI-1 gene expression is conserved evolutionarily and may act as a key regulator of the apoptotic pathway in BAC.

Adenocarcinoma↗

Neuroendocrine neoplasms of the lung: a prognostic spectrum.

PURPOSE: Neuroendocrine (NE) tumors of the lung include typical carcinoid (TC), atypical carcinoid (AC), large-cell NE carcinoma (LCNEC), and small-cell lung carcinoma (SCLC). Their clinicopathologic profiles and relative grade of malignancy have not been defined. PATIENTS AND METHODS: From 10 Japanese institutes, 383 surgically resected pulmonary NE tumors were collected. The histologic diagnosis was determined by the consensus of a pathology panel consisting of six expert pathologists as TC, AC, LCNEC, or SCLC on the basis of the WHO classification, and its relationship to clinicopathologic profiles was analyzed. RESULTS: Of the 383 tumors, 18 were excluded because of an improper specimen. The pathology panel reviewed the remaining 366 tumors, and a diagnosis of NE tumor was made in 318 patients (87.4%); 55 patients had TC, nine had AC, 141 had LCNEC, and 113 had SCLC. The 5-year survival rates of patients with all stages were as follows: 96.2% for TC, 77.8% for AC, 40.3% for LCNEC, and 35.7% for SCLC. There was significant prognostic difference between TC and AC as well as between AC and LCNEC+SCLC. However, there was no difference between LCNEC and SCLC, and their survival curves were superimposed. The multivariate analysis indicated that histologic type, completeness of resection, symptoms, nodal involvement, and age were significantly prognostic. CONCLUSION: The grade of malignancy of NE tumors was upgraded in the following order: TC, AC, LCNEC, and SCLC. No prognostic difference was noted between LCNEC and SCLC. The high-grade NE histology uniformly indicated poor prognosis regardless of its histologic type.

Carcinoma, Small Cell↗

Effectiveness of steroid treatment for hoarseness caused by idiopathic fibrosing mediastinitis: report of a case.

A 65-year-old woman was referred to our department for investigation and treatment of hoarseness. A chest computed tomography (CT) scan showed a mediastinal mass spreading into the aortopulmonary window. This finding and that of flexible laryngoscopy suggested that the hoarseness was being caused by left recurrent nerve involvement resulting in left vocal cord paralysis. Thus, we performed a mediastinoscopic biopsy via a parasternal incision. Pathological examination revealed dense fibrous tissue infiltrated with varied inflammatory cells. Because no etiological pathogen or neoplastic lesion was identified, we diagnosed idiopathic fibrosing mediastinitis and began treating the patient with prednisolone. After a course of treatment, the mediastinal lesion showed a remarkable response. The hoarseness resolved as the lesion became smaller. Laryngoscopy confirmed recuperation of vocal cord function. This report shows that steroid therapy is a treatment option for hoarseness caused by recurrent laryngeal nerve involvement of fibrosing mediastinitis, if administered under close observation.

Aged↗

Predictive factors for the histologic response to preoperative radiotherapy in advanced oral cancer.

PURPOSE: Preoperative radiotherapy and chemotherapy are important in treating advanced oral cancer. We attempted to elucidate predictive factors for the histologic response to preoperative radiotherapy or chemoradiotherapy. PATIENTS AND METHODS: Forty-three patients with locally advanced cancer of the oral cavity and oropharynx were treated preoperatively with radiotherapy (50 Gy); surgery included modification of the resected area to preserve organ function. RESULTS: Hemoglobin level and histologic differentiation were independent factors significantly associated with the histologic response by multivariate analysis. Locoregional failure occurred only in patients with poor histologic response, and there was a significant difference in the 5-year survival rate between patients with good and poor responses (84% vs 32%). Multivariate analysis indicated that the histologic response at the primary site and the number of metastatic lymph nodes were prognostic factors. CONCLUSION: We identified predictive factors for a good response to preoperative therapy and found a high survival rate in patients with a good response.

Adult↗

Pathologic findings of lung tumors diagnosed on baseline CT screening.

Sixty-five people had a resection of their baseline screen-diagnosed lung cancers in the Early Lung Cancer Action Program. Forty-nine of the carcinomas were solitary, and 42 of these were adenocarcinomas. More than 1 carcinoma was found in 16 patients after pathologic examination of the lobectomy specimen; 15 of the 16 second carcinomas were adenocarcinomas, mixed subtype. Eighteen cases were submitted by local pathologists as Bronchioloalveolar carcinomas but were found to be invasive adenocarcinomas according to the World Health Organization classification by the Pathology Review Panel. Of the 65 resected cases, 57 were N0, 7 were N1, and 1 was N2. Upon careful review of the lobectomy specimens, 49 cases had solitary malignancies, 30 were Stage IA, 13 Stage IB, 3 Stage IIA, 2 Stage IIB, and 1 Stage IIIA on the basis of the American Joint Committee on Cancer/International Union for Cancer Control criteria. In the 16 cases found to have multiple malignancies, 6 had histologically different carcinomas and the remaining 10 had histologically identical malignancies. Eighty-three percent (76/92) of the carcinomas invaded the stroma with destruction of normal lung, and 21% (19/92) also showed either pleural or angiolymphatic invasion, even though 88% (57/65) of the carcinomas were free of lymph node metastases. This report describes the pathologic findings of the resected cases. Histopathologic distinctions among atypical adenomatous hyperplasia, bronchioloalveolar carcinomas, and invasive adenocarcinoma are described in detail.

Aged↗

Phenotypic characterization of endometrial stromal sarcoma of the uterus.

Endometrial stromal sarcoma (ESS) of the uterus is a rare uterine malignancy that has not been characterized in detail. To characterize the phenotype of ESS of the uterus, we extracted RNA from ESS and the stroma of normal endometrium using a tissue microdissection system and compared the expression profiles in the two tissues. After suppression subtractive hybridization and differential screening, we detected the metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) gene as one of the major genes upregulated in ESS, and a full-length placental cDNA clone (CS0DI066YJ10) as one of the major genes downregulated. The results were confirmed by in situ hybridization in four resected specimens of ESS and 36 biopsy specimens of normal endometrial tissue. All ESS (4/4) and all cases of endometrial stromal cells in the proliferative phase (13/13) were positive for MALAT-1, but samples of normal stroma in the secretory phase and menopausal state included some that were negative or weakly positive for MALAT-1 (5/13 and 3/10, respectively). In contrast, all ESS and 12 of 13 cases of stromal cells in the proliferative phase were negative for the full-length placental cDNA clone but 10 of 13 cases of endometrial stromal cells in the secretory phase were positive for transcripts of the gene (P < 0.05). These results indicated that endometrial stromal cells have different phenotypic characteristics between proliferative and secretory phases and the tumor cells of ESS have the phenotypic character of endometrial stromal cells in the proliferative phase.

Cell Proliferation↗

Characteristics of loss of heterozygosity in large cell neuroendocrine carcinomas of the lung and small cell lung carcinomas.

Large cell neuroendocrine carcinoma (LCNEC) of the lung is a new entity. Besides morphological characteristics, its molecular biological features have been investigated by many researchers and compared to those of other neuroendocrine carcinomas, small cell lung carcinoma (SCLC) and carcinoid tumor (CT). However, there are few reports that show the significantly different genetic characteristics between them. The purpose of the present paper was to study the frequency of loss of heterozygosity (LOH) at chromosome 3p (3p14.2) in 38 neuroendocrine carcinomas of the lung (13 LCNEC, 11 SCLC and 14 CT) and 10 large cell carcinomas (LCC). The frequencies of LOH at 3p14.2 were 69.2% in LCNEC, 81.8% in SCLC, 50.0% in LCC and 7.14% in CT. Those at 22q13.3 were 30.8% in LCNEC, 72.7% in SCLC, 45.5% in LCC and 7.14% in CT. In particular, the frequency of SCLC with LOH at both 3p14.2 and 22q13.3 (63.6%) was significantly higher than that of LCNEC (15.4%). LCNEC and SCLC had different characteristics of LOH patterns at 3p14.2 and 22q13.3. The combined analysis of the LOH at 3p14.2 and 22q13.3 is thought to be useful for differential diagnosis between LCNEC and SCLC.

Biomarkers, Tumor↗

Evolving concepts in the pathology and computed tomography imaging of lung adenocarcinoma and bronchioloalveolar carcinoma.

PURPOSE: To review recent advances in pathology and computed tomography (CT) of lung adenocarcinoma and bronchioloalveolar carcinoma (BAC). METHODS: A pathology/CT review panel of pathologists and radiologists met during a November 2004 International Association for the Study of Lung Cancer/American Society of Clinical Oncology consensus workshop in New York. The purpose was to determine if existing data was sufficient to propose modification of criteria for adenocarcinoma and BAC as newly published in the 2004 WHO Classification of Lung Tumors, and to address the pathologic/radiologic concept of diffuse/multicentric BAC. RESULTS: Solitary small, peripheral BACs have an excellent prognosis. Most lung adenocarcinomas with a BAC pattern are not pure BAC, but rather adenocarcinoma, mixed subtype with invasive patterns. This applies to tumors presenting with a diffuse/multinodular as well as solitary nodule pattern. The percent of BAC versus invasive components in lung adenocarcinomas appears to be prognostically important. However, a consensus definition of "minimally invasive" BAC with a favorable prognosis could not be achieved. While recognition of a BAC component is possible, the diagnosis of BAC with exclusion of invasive adenocarcinoma cannot be made by small biopsy or cytology specimens. CONCLUSION: There is a need to work toward a mutual understanding and consensus between pathologists, clinicians, and researchers with the use of the term BAC versus adenocarcinoma. Future studies should make some attempt to quantitate these components and/or other features such as size of scar, size of invasive component, or pattern of invasion. Hopefully, this work will allow definition of a category of adenocarcinoma, mixed subtype with predominant BAC/minimal invasion and a favorable prognosis.

Adenocarcinoma↗

Loss of function of p16 gene and prognosis of pulmonary adenocarcinoma.

BACKGROUND: Stepwise progression of peripheral-type lung adenocarcinoma was characterized morphologically and was related to prognosis. Expression of the tumor suppressor gene p16 in pulmonary adenocarcinoma decreased, mainly as a result of aberrant methylation of the CpG islands of the promoter region. METHODS: Aberrant methylation status of the p16 promoter region, the expression of its product, and loss of heterozygosity (LOH) on 9p21 were examined in surgically resected lung specimens from 57 patients (28 males and 29 females) with peripheral-type lung adenocarcinoma measuring </= 2 cm in diameter. RESULTS: Aberrant methylation of the p16 promoter region, negative p16 protein expression, and LOH of the 9p21 region were detected in 40.4%, 50.9%, and 40.4% of tumor samples, respectively. The alterations of the p16 gene were associated with poor prognosis, and in particular the prognosis of patients with aberrant p16 methylation was significantly worse than that of patients without aberrant methylation. These alterations also were associated with morphologic classification into bronchioloalveolar carcinoma (BAC) and non-BAC adenocarcinoma. Both aberrant methylation and LOH of 9p21 were associated with negative protein expression, but the former was correlated more closely with loss of function than was the latter. Cases with both alterations were completely negative for expression of the p16 gene product. CONCLUSIONS: Aberrant methylation of the promoter region of the p16 gene and loss of expression of its product were in accord with the multistep progression of peripheral-type lung adenocarcinoma, and these alterations were associated closely with poor prognosis of the disease.

Adenocarcinoma↗

Prognostication of small-sized primary pulmonary adenocarcinomas by histopathological and karyometric analysis.

To reveal useful prognostic factors in cases of small-sized pulmonary adenocarcinoma, we conducted a histological and karyometric analysis of 116 small-sized pulmonary adenocarcinomas measuring less than 2 cm in maximum diameter and four specimens of atypical adenomatous hyperplasia (AAH). The small-sized pulmonary adenocarcinomas were classified by using criteria described previously [Noguchi M, Morikawa A, Kawasaki M, et al. Small adenocarcinoma of the lung. Histologic characteristics and prognosis. Lung Cancer 1995:75;2844-52]. There were 99 tumors of replacement-type adenocarcinoma, comprising 11 type A, localized bronchioloalveolar adenocarcinoma (LBAC); 6 type B, LBAC with alveolar collapse; and 82 type C, LBAC with foci of fibroblastic proliferation. The 17 remaining tumors were non-replacement-type adenocarcinomas. Among the potential prognostic factors examined, histological subtype was the most closely correlated with 5-year relapse-free survival rate. Furthermore, in patients with type C adenocarcinomas, a small fibroblastic proliferation (F) to fibrosis area (f) ratio (F-f ratio) (<10%) of the tumor and a small maximum nuclear diameter (Max ND; <13.50 microm) of tumor cells were closely associated with an excellent prognosis. Histological subtypes of type A and B adenocarcinomas, a small F-f ratio, and a small Max ND of type C adenocarcinomas were closely correlated with an excellent prognosis in small-sized adenocarcinoma.

Adenocarcinoma↗