Stratifying the risk of lymph node metastasis in undifferentiated-type early gastric cancer.

AIM: To study how lymph node metastasis (LNM) risk is stratified in undifferentiated-type early gastric cancer (undiff-EGC) dependent on combinations of risk factors. METHODS: Five hundred and sixty-seven cases with undiff-EGC undergoing gastrectomy with lymphadenectomy were examined retrospectively. Using clinicopathological factors of patient age, location, size, an endoscopic macroscopic tumor form, ulceration, depth, histology, lymphatic involvement (LI) and venous involvement (VI), LNM risk was examined and stratified by conventional statistical analysis and data-mining analysis. RESULTS: LNM was positive in 44 of 567 cases (7.8%). Univariate analysis revealed > 2 cm, protrusion, submucosal (sm), mixed type, LI and VI as significant prognostic factors and > 2 cm and LI-positive were independent factors by multivariate analysis. In preoperatively evaluable factors excluding LVI, sm and > 2 cm were independent factors. According to the depth and size, cases were categorized into the low-risk group [m and ≤ 2 cm, 0% (LNM incidence)], the moderate-risk group (m and > 2 cm, 5.6%; and sm and ≤ 2 cm, 6.0%), and the high-risk group (sm and > 2 cm, 19.3%). On the other hand, LNM occurred in 1.4% in all LI-negative cases, greatly lower than 28.2% in all LI-positive cases, and LNM incidence was low in LI-negative cases even in the moderate- and high-risk groups. CONCLUSION: LNM-related factors in undiff-EGC were depth and size preoperatively while those were LI and size postoperatively. Among these factors, LI was the most significantly correlated factor.

Invasive ductal carcinoma arising from an ectopic pancreas in the gastric wall: a long-term survival case.

A case of invasive ductal carcinoma of an ectopic pancreas in the stomach in a 74-year-old woman is presented. A 4.0 cm gastric submucosal tumor (SMT) was resected surgically. Histologically, the tumor showed cystic tissue consisting of an ectopic pancreas with foci of a moderately differentiated tubular adenocarcinoma. In this tumor, small pancreatic tissues, acini, Langerhans islets, and ductular cells were detected in the gastric SMT. The patient has experienced long-term survival. The incidence of pancreatic cancer of an ectopic pancreas is rare, and the etiology of this disease is discussed in the literature.

Expression of human pendrin in diseased thyroids.

We examined pendrin expression in various diseased thyroid tissues by immunohistochemistry (IHC) using antiserum raised against human pendrin and by real-time quantitative RT-PCR. In normal thyroids the antiserum reacted with the apical membrane of follicular cells and its immunoreactivity was faint. In Graves' thyroids, the IHC expression of pendrin appeared in a pattern similar to that of normal thyroids but it was more extensive and stronger, especially in areas showing marked proliferation of follicular cells. The immunoreactivities of pendrin in nodular goiters varied from case to case. In follicular adenomas, pendrin was localized in the follicle-forming parts of the tumor but was negative in trabecular parts. Pendrin was negative in all follicular carcinomas, papillary carcinomas, and in one case of medullary carcinoma. In quantitive mRNA analysis, the relative values of pendrin mRNA were significantly low in papillary carcinoma (p<0.01), whereas the values in other diseased thyroids were not significantly different from those in normal thyroids. These results suggest that pendrin may play a role in thyroid hormone production as the apical porter of chloride/iodide and investigation of pendrin leads to a better understanding of functional aspects of the iodine transportation system in thyroid diseases.

Expression of thyroid transcription factor-1 in normal and neoplastic lung tissues.

The expression of thyroid transcription factor-1 in normal and neoplastic tissues and cell lines of the human lung was investigated using immunohistochemistry and in situ hybridization in conjunction with reverse transcription polymerase chain reaction. In normal lung tissues, immunoproducts of thyroid transcription factor-1 were observed in the nuclei of alveolar cells and bronchiolar cells. Interestingly, in distal bronchioles, immunohistochemistry and in situ hybridization revealed that thyroid transcription factor-1 was present not only in nonciliated cells (Clara cells) but also in ciliated cells and basal cells. In neoplastic tissues, thyroid transcription factor-1 was demonstrated in adenocarcinomas and small cell lung carcinomas with high frequency: 96% and 89% of cases, respectively. Thyroid transcription factor-1 was not detected in squamous cell carcinomas and large cell carcinomas. The strong immunoreactivity of thyroid transcription factor-1 or simultaneous expressions of thyroid transcription factor-1 and surfactant protein A tended to correlate with the differentiation phenotypes in adenocarcinomas; they were more frequently present in the well-differentiated type than were moderately and/or poorly differentiated types. By reverse transcription polymerase chain reaction, expression of thyroid transcription factor-1 messenger RNA was observed in squamous cell carcinomas in addition to in adenocarcinomas and small cell lung carcinomas, and this finding was confirmed in the cell lines from squamous cell carcinomas. Only one case of 99 adenocarcinomas that originated in various organs other than lung and thyroid immunohistochemically expressed thyroid transcription factor-1. Our results suggest that thyroid transcription factor-1 can play an important role for the maintenance and/or differentiation process in bronchiolar and alveolar cells. Thyroid transcription factor-1 expression associates with histologic types and/or differentiation of lung cancers and can be a valuable marker for the better understanding of their biological nature and pathological behavior.

Mutation of ras oncogene in di-isopropanolnitrosamine-induced rat thyroid carcinogenesis.

To clarify the role of ras gene mutation in thyroid tumorigenesis, DNAs extracted from various rat thyroid lesions induced by di-isopropanolnitrosamine (DIPN) administration were analyzed using the microdissection-polymerase chain reaction-direct sequence (MD-PCR-DS) method. The MD-PCR-DS method revealed that K- ras gene mutation (G-A transition at codon 12) was frequently detected in nodular lesions (incidence of mutation 75%) and absent in diffuse hyperplastic and pre-nodular lesions. Although the incidence of mutation in nodular lesions was not correlated with the histological type (type 2A 76%; type 2B 84%; and type 3 71%) or treatment period (15 weeks 84% and 30 weeks 71%), it was correlated with the administration method (single injection 55% and serial injection 91%). In conclusion, K- ras mutation plays an important role in DIPN-induced rat thyroid tumorigenesis, possibly regarded as an early event in the tumorigenic process.

Effects of Propyithiouracil (PTU) Administration on the Synthesis and Secretion of Thyroglobulin in the Rat Thyroid Gland: A Quantitative Immuno-electron Microscopic Study Using Immunogold Technique.

To clarify the effects of an antithyroid drug on the kinetics of thyroglobulin synthesis, secretion, and reabsorption in the thyroid follicles, propylthiouracil (PTU) was administered to rats and the thyroid glands were examined by a refined post-embedding immunogold technique during and after withdrawal of PTU. Seven-wk-old male Wistar rats were administered with S mg of PTU/d through a gastric tube, and sacrificed at 1 and 2 wk of administration and at 1, 2, and 3 d, and 1, 2, 3, and 4 wk, after discontinuation. The administration of PTU caused a remarkable dilatation of the rER and Golgi apparatus, but these areas gradually recovered after withdrawal of PTU. During the experiment, no significant change in the density of thyroglobulin (Tg) was observed except for a transient increase immediately after withdrawal of PTU. The expression of Tg on subapical vesicles (SV) and follicular colloid took a relatively parallel course; increasing during administration of PTU and decreasing with a transient peak immediately after treatment was discontinued. In contrast to the remarkable changes in the morphology of compartments involved in Tg synthesis, the development of colloid droplets and formation of secondary lysosomes were suppressed during and after discontinuing administration of PTU. However, the basic pattern of the gradient of Tg density among the cellular compartments was essentially retained in the experimental group. Thus the present immunoelectron-microscopic study provided evidence that administration of PTU stimulates the synthesis and secretion of Tg in the follicular epithelium in vivo, and, also, suppresses reabsorption and degradation of Tg. Further, it was speculated that the density gradient of Tg among the compartments involved in Tg synthesis, secretion and storage is regulated by an unknown constitutive mechanism and not by the thyroid-stimulating hormone (TSH)-TSH receptor-mediated system.

Immunohistochemical and immunoelectron microscopical localization of procollagen III peptide in papillary carcinoma of thyroid.

The immunohistochemical localization of procollagen III peptide, a precursor of type III collagen, was examined in 38 papillary carcinomas and 25 follicular neoplasms using an immu-noperoxidase technique. Although localization of procollagen ill peptide was not demonstrated in normal follicular cells, distinct cytoplasmic immunostaining of neoplastic cells was frequently found in the tissues examined, as were stromal fibroblasts. Such cytoplasmic immunostaining was observed in 92.1 % of 38 papillary carcinomas and in 36.0% of 25 follicular neoplasms. Cytoplasmic immunoreactivity in papillary carcinomas was more intense at the peripheral zone of the tumor and correlated with the degree of invasiveness. The controls, in which the primary antibody was preabsorbed with procollagen ill peptide or replaced with normal rabbit serum, showed only faint background staining in all specimens. Immunoelectron microscopical examination revealed that electron-dense deposits, indicating procollagen III peptide, were located in the perinuclear space, Golgi apparatus, and rough endoplasmic reticulum of papillary carcinoma cells. These results suggest that neoplastic cells, especially papillary carcinoma cells, could play an important role in type III collagen production, possibly in connection with the creation of an environment that is conducive to their progression.