Pathology International

Ohtani, Haruo

doi: 10.1111/j.1440-1827.1998.tb03820.xpmid: 9589457

Cancers are characterized by invasive growth and distant metastasis. Cancer cells not only destroy the pre‐existing extracellular matrix, but cancer invasion per se usually induces new matrix formation by activation of stromal cells; that is, desmoplastic reaction. This process includes both matrix production and degradation; that Is, the remodeling process. The similarity between desmoplastic reactions in cancer stroma and the wound healing process has already been pointed out, and it has been well documented that matrix‐degrading processes are actively involved In the wound healing process. A recent study revealed that most matrix‐degrading enzymes, generally considered to be one of the main mechanisms of cancer invasion and metastasis, are originated from stromal cells. Based on these preconditions, the present review postulates that the abundant expression of matrix‐degrading enzymes by fibroblasts, coupled with the abundant expression of type I procollagen, is involved in the matrix remodeling processes occurring in cancer stroma; that is, the mechanism similar to the wound healing process. Next, macrophages distributed along the invasive margin are known to express matrix‐degrading enzymes/factors. Data from past studies of colon carcinoma indicate that the tissue expression of matrix metalloproteinase‐9 and urokinase‐type plas‐mlnogen activator receptor Is inversely associated with simultaneous liver metastasis and infiltrating growth pattern. Previous clinicopathologic data have indicated that immune/Inflammatory cells are one of the factors for a favorable prognosis. This suggests that the expression of matrix‐degrading enzymes/factors by these host cells may be involved in host immune/inflammatory reactions, and that the net function of these cells can be defensive towards the host. Data from past studies of colon carcinoma on the expression of the intercellular adhesion molecule‐1 suggest that the interaction between macrophages, lymphocytes, and the phenotypes of venules distributed along the Invasive margin, further support the pro‐inflammatory milieu there. Therefore, the matrix degradation process in cancer tissue is multifunctional: besides the Involvement in cancer invasion and metastasis, the matrix degradation process is also involved in the tissue remodeling process and in the immune/inflammatory reaction occurring in the stroma.

Nozawa, Yoshihiro; Wakasa, Haruki; Abe, Masafumi

doi: 10.1111/j.1440-1827.1998.tb03821.xpmid: 9589458

To elucidate the relationship between Reed‐Sternberg (R‐S) cells and background T cells, the expression of CD80 and CD86 of R‐S cells in Hodgkin's disease (HD), and the ligand CD28 expression and the MIB‐1 index of background T cells were immunohistochemically investigated. CD80 and CD86 were found to be expressed on R‐S cells in almost all cases of HD. CD28 was expressed with strong intensity on many background T cells around R‐S cells. The MIB‐1 index of background T cells was 30.3% (range, 15.5–38.9%) and was much higher than 10.9% (range, 9.8–11.7%) in B cell lymphomas. These results suggest that the interaction between CD80 and CD86 on R‐S cells, and CD28 on background T cells may induce T cell proliferation and be associated with tumor mass of HD.

Oka, Takashi; Sarker, Ashit Baran; Teramoto, Norihiro; Yoshino, Tadashi; Akagi, Tadaatsu

doi: 10.1111/j.1440-1827.1998.tb03822.xpmid: 9589459

Accumulation of the p53 protein has been found In several types of lymphomas. However, p53 gene mutations have been infrequently demonstrated in some specific types of lymphomas. In the present study, a correlation between p53 immunoreactivity and p53 gene mutations in a large panel of non‐Hodgkin's lymphoma (NHL) cases is attempted. A panel of 202 cases of NHL was evaluated by immuno‐hlstochemical staining for p53 protein. All cases that were immunohistochemically positive for p53 protein were analyzed by the polymerase chain reaction (PCR) single strand conformation polymorphism (SSCP) method to identify mutations within the pS3 gene. In order to confirm the mutation, sequencing of PCR‐amplified p53 gene segments was performed. Overexpression of p53 protein was found in 59 of the 202 cases of NHL, but only four of these 59 cases showed a shift on SSCP analysis, and point mutations were detected in three of them by the subsequent sequencing. p53 Immunoreactivity was generally greater in high‐grade lymphoma. The results of this study suggest that Immunohistochemlcal reactivity for p53 protein is not a reliable Indicator of the presence of their structural alterations of p53 gene exons 4–9 in NHL.

Kubota, Tetsuo; Mlyauchl, Motohiro; Miura, Keljl; Hirokawa, Goh; Awaya, Akira; Miyasaka, Nobuyuki; Kurosawa, Yoshikazu; Kanal, Yoshiyukl; Maruyama, Koshi

doi: 10.1111/j.1440-1827.1998.tb03823.xpmid: 9589460

Nucleobindin (Nuc) was originally found to be an enhancement factor of antl‐DNA antibody production secreted by a lymphold cell line derived from a lymphoprollferatlve MRL/Ipr mouse. It has been shown that Nuc has a unique structure containing a DNA‐ and two calcium‐binding domains, and a leuclne zipper motif, but Its biological roles have not yet been fully elucidated. Expression of Nuc was first studied in human lymphocytes. Expression of Nuc mRNA in normal peripheral blood mononuclear cells was significantly increased upon mitogen stimulation. Anti‐human Nuc monoclonal antibody H‐1D8 immunopreclpitated Nuc protein in the nuclear extract of Molt‐4 cells. Furthermore, in the immunohlstochemlcaf staining of tumor specimens from 108 patients with non‐Hodgkin's lymphoma (NHL) with H‐1D8, H‐1D8‐posltlve cells were observed in nearly all cases in varying frequency. According to the Working Formulation, the percentage of cases in which more than 90% of the tumor cells were stained with H‐1D8 was 65% in the high grade of the histological malignancy, 54% In the Intermediate grade, and 22% in the low grade; however, normal ceils surrounding the tumor cells were virtually negative for H‐1D8. These results showed that the level of Nuc expression in human lymphocytes reflects the status of activation or proliferation of the cells, thus providing a clue for the further investigation into biological roles of Nuc. In addition, It might be applicable to the clinlcopathological estimation of NHL as a novel Indicator.

Wakasa, Kenichi; Haba, Tomoko; Sasaki, Masaomi; Sakurai, Masami; Ikebe, Takashl; Shuto, Taichi; Hirohashi, Kazuhiro; Kinoshita, Hiroaki

doi: 10.1111/j.1440-1827.1998.tb03824.xpmid: 9589461

In the cirrhotic and precirrhotic liver, there may be small foci with increased cellularity and amphophilic cytoplasm. These are microscopic lesions that do not form macroscopically detectable nodules, which differ from the macroscopically apparent nodules of dysplastic nodules. In the present study, we assessed the proliferating activity of 12 hyperplastic foci in 11 patients with cirrhosis or chronic hepatitis, by staining for agyrophilic nucleolar organizing regions (AgNOR). The mean AgNOR count per nucleus in the hyperplastic foci ranged from 0.96 to 1.36 (mean, 1.13; SD 0.12), and from 0.81 to 1.06 (mean, 0.94; SD 0.08) in the controls. The AgNOR count In the hyperplastic foci was significantly higher than that In the controls (P> 30.01). Small hyperplastic foci show Increased proliferative activity. Further study on these foci is required to clarify their relation to hepatocarcinogenesis.

Fukushlma, Noriyoshi; Suzuki, Miwako; Fukayama, Masashi

doi: 10.1111/j.1440-1827.1998.tb03825.xpmid: 9589462

To develop an objective reference for the cytological evaluation of atypical cells in bile and pancreatic juice, we analyzed K‐ras oncogene mutation In atypical cell clusters, which were collected directly from cytological smear slides; 50 samples (cell clusters) from 31 smear slides of 21 patients with carcinomas of the pancreatic head region, and nine samples from eight cases of benign disease. These cell clusters (5–1000 cells/cluster) were selectively suspended In buffer containing proteinase K, and subjected to DNA extraction. K‐ras codon 12 mutation was determined by polymerase chain reaction amplification, followed by digestion with BstNI. The K‐ras gene was amplified in 20 of 21 cases with carcinoma (34/50 samples), and In seven of eight cases with non‐neoplastic disease (8/9 samples). Among the cases of which primary tumors showed K‐ras mutation, amplification was successful in 10 of 11 cases; mutation was demonstrated in three of seven cases with cytologically atypical cells (4/11 samples), and in three of three cases with cytologically malignant cells (5/7 samples). No mutation was Identified in the 10 cases of carcinoma without K‐ras mutation (0/15 samples), or in eight cases of non‐neoplastlc disease (0/8 samples). Cytological details could be comparatively evaluated between atypical cell clusters with or without mutation on the same smear slides in two cases. This type of direct analysis of atypical cell clusters may be useful in the self‐assessment of cytological diagnosis of bile and pancreatic juice.

Masuda, Mitsunobu; Takano, Yasuo; Iki, Masayuki; Asakura, Tomoyuki; Hashiba, Takafumi; Noguchi, Sumio; Hosaka, Masahiko

doi: 10.1111/j.1440-1827.1998.tb03826.xpmid: 9589463

The prognostic significance of Ki‐67, p53, and Bcl‐2 expression was evaluated in prostate cancer patients with lymph node metastases. Immunohistochemical staining of archived material obtained from 56 patients was performed by the streptavldin‐biotin method. Univariate survival analysis showed that a Ki‐67 labeling index (Ki‐67 LI) of ≥8.4 in the primary tumor identified a group of patients with a significantly poorer prognosis (P<0.001). Furthermore, a Ki‐67 LI of ≥8.7 in the nodal metastatlc tumor was also associated with a poorer prognosis (P<0.01). Multivariate analysis showed that the Ki‐67 LI of primary tumors (P<0.01) and lymph node metastases (P<0.01) had independent prognostic value. p53 and Bcl‐2 expression had no prognostic value in patients with prostate cancer and lymph node involvement. The Ki‐67 LI has more prognostic value than p53 and Bcl‐2 expression for patients with prostate cancer that has spread to the lymph nodes.

Fukasawa, Yuichiro; Takada, Akio; Tateno, Masatoshi; Sato, Hidetoshi; Koizumi, Makoto; Tanaka, Akihiko; Sato, Tei

doi: 10.1111/j.1440-1827.1998.tb03827.xpmid: 9589464

A case of malignant solitary fibrous tumor (SFT) is reported, occurring in a 61‐year‐old man with frequent hypoglycemia. Endocrinological analyses showed high serum levels of insulin‐like growth factor II (IGF‐II) and suppressed secretion of insulin. After the removal of a pleural tumor, which weighed 3150g, serum IGF‐II levels returned to normal and hypoglycemic attacks ceased. The tumor was composed of uniform spindle cells arranged in bundles, and fascicles with varying amounts of collagen and retlculin fibers. Mitotlc figures at the rate of 6/10 high‐power fields, and frequent foct of necrosis and hemorrhage were seen. Almost all of the tumor cells were Immunohlstochemically positive for vimentin and CD34. Electron microscopy revealed the immature mesenchymal or myofibroblastic nature of the tumor cells. These findings are consistent with malignant SFT of the pleura. Moreover, the tumor produced IGF‐II mRNA as demonstrated by northern blot analysis. Thus, hypoglycemia of this patient was induced by SFT through the production and secretion of IGF‐II.

Kimura, Yoko; Matsumae, Mitsunori; Tsutsumi, Yutaka

doi: 10.1111/j.1440-1827.1998.tb03828.xpmid: 9589465

Myxold meningioma seen In a 25‐year‐old man is presented. Hlstologlcally, Leu 7‐positive meningotheliomatous tumor cells were embedded in the alclanophilic myxoid matrix. Characteristically, eosinophilic granular deposition was detected around the tumor cells and the boundary of tumor cells was not clearly defined. The pericellular deposits revealed the nature of the basement membrane with positive reactions by periodic acid‐Schlff (PAS) sequence and immunostaining for type IV collagen, which is the major structural component of basement membrane. However, laminin, which is a non‐collagenous glycoprotein of the basement membrane, was undetectable, and silver was not impregnated. Similar abnormal deposition of PAS‐positive basement membrane‐like material was observed in the myxoid stroma of a microcystic meningioma among 72 meninglomas additionally examined. The significance of the discrepant localization of immunoreactive type IV collagen and laminin is discussed.

Nakamura, Shin‐lchl; Kuroda, Tuguhisa; Sugai, Tamotsu; Ono, Sadahide; Yoshida, Toru; Akasaka, Iichiro; Nakashima, Fumie; Sasou, Shunichl

doi: 10.1111/j.1440-1827.1998.tb03829.xpmid: 9589466

A 65‐year‐old Japanese male consulted Ozuchi Prefectural Hospital (Iwate, Japan) on 19 January 1994 complaining of weight loss. Cecal mucosal biopsy material, which was stained with hematoxylln‐eosin revealed a thick, basophllic fuzzy fringe covering the surface epithelium. Transmission and scanning electron microscopy observations demonstrated the presence of slightly wavy spirochaetes with tapered ends, which were attached to the surface epithelium of the colonlc mucosa via one of these ends. The patient did not display any clinical symptoms of Inflammatory bowel disease, and laboratory tests eliminated an Immunodeficiency condition. Thus, in the present case, the Intestinal spirochaetes appear to be harmless commensals. This paper presents the first reported case of Intestinal spirochaetosis fn Japan.