AgNOR quantity as a prognostic tool in hyperplastic and neoplastic parathyroid glands

Prediction of evolution of secondary hyperplasia and tumours of the parathyroid glands is still a problem in histopathology. To assess whether the quantity of silver-stained nucleolar organiser region (AgNOR) proteins might be used as a prognostic tool in parathyroid pathology, a standardised AgNOR analysis has been performed on 19 cases of parathyroid hyperplasia caused by secondary hyperparathyroidism (PH), 8 cases of adenoma (PA) and 10 cases of carcinoma (PC). Clinico-pathological data and follow-up information were available. On formalin-fixed and paraffin-embedded sections, the visualisation and quantification of AgNORs were achieved according to the 1995 guidelines of the Committee on AgNOR Quantification. Then, the mean area (square micrometres) of AgNORs per nucleus (NORA) was evaluated by means of an image analyser and specific softwares. After testing the normal distribution of NORA values, statistical parametric tests were utilised; Kaplan-Meier and Cox multivariate analyses were also performed. In parathyroid lesions, a progressive increase of mean NORA values was observed from PH (2.895 μm²; SE 0.171) through PA (3.638 μm²; SE 0.125) to PC (4.701 μm²; SE 0.179); these differences were highly significant (P<0.001), although some degree of overlap was found among single NORA values. A significantly higher mean NORA value was revealed in PC with distant metastases than was noted in cases with no current clinical evidence of disease progression. Furthermore, a significantly (P<0.001) higher mean NORA value was encountered in the group of PH with recurrences (3.600 μm²; SE 0.106) than in nonrecurrent PH (2.261 μm²; SE 0.087). Multivariate analyses indicated that the NORA value was an independent prognostic parameter determining the risk of recurrence in PH. We suggest that AgNOR quantity may be a promising additional tool for predicting the biological behaviour of parathyroid lesions. Received: 2 December 1999 / Accepted: 1 March 2000     

The role of the Epstein-Barr virus in the oncogenesis of EBV(+) gastric carcinomas

 Five hundred and thirteen cases of gastric carcinoma were investigated for the presence of viral RNA, and the clinico-pathological data, geno-type, BamHIF restriction fragment polymorphism (RFLP) and specific LMP-1 30 bp gene deletion were also examined. EBVs detected in lymphocytes in 20 normal gastric mucosa, 7 lymphoma cell lines (LCLs) maintained in severe combined immunodeficiency (SCID) mice and 18 non-Hodgkin’s lymphomas were compared with those in the gastric carcinoma cases. Thirty-three cases (6.4%) were demonstrated to be positive for EBV by means of EBER-1 RNA in situ hybridization. Clinico-pathological data showed no statistically significant difference in histological grading, location of cancer and status of vessel and lymphatic invasion between the EBV-positive and -negative groups, although the former significantly predominated in the submucosal invasion group (submucosal vs mucosal P=0.021; submucosal vs advanced cancer P=0.033). Some of these data were different from corresponding data in earlier reports. In cases that were evaluated by molecular biology, type A, wild-type F and LMP-1 gene deletion predominated except one in 21 informative cases, one in 24 and two in 16, respectively. EBVs detected in lymphocytes in normal gastric mucosa, LCLs in SCID mice and non-Hodgkin’s lymphoma were also predominantly affected by type A, wild-type F and LMP-1 gene deletion with few exceptions. The results indicate a lack of genetic differences among EBVs in gastric carcinoma, normal population, LCLs of SCID mice and non-Hodgkin lymphomas. Some EBV infections in gastric carcinomas may be transient, especially in the submucosal invasion group. Received: 7 July 1998 / Accepted: 24 September 1998     

Prognostic significance of apoptosis and associated factors in oral squamous cell carcinoma

Tumour progression is characterised by an imbalance between cell proliferation and apoptosis. The aim of our study was to estimate the importance of proliferation and apoptosis associated parameters in primary squamous cell carcinomas (SCCs) of the oral cavity and oropharynx. For determination of apoptosis, the enzymatic labelling of DNA fragmentation with a terminal transferase reaction was used in 156 tissue samples of 107 patients, including corresponding lymph-node metastases in nine cases. P53, bcl-2, and Ki-67 were determined immunohistologically. P53 was detectable in 50.5% of the cases. Positive staining was associated significantly with decreased apoptosis (P<0.003). Bcl-2 was upregulated in 31.8% of the cases depending on the tumour grading (P<0.001) and correlated negatively with apoptosis (P<0.001). Proliferation (P<0.006) and apoptosis (P<0.03) were enhanced in larger tumours, though a direct correlation between these two parameters was not proven. Nevertheless, in contrast to the conventional tumour staging and grading, neither the expression of p53 or bcl-2 nor the apoptosis or Ki-67 measurements were able to predict survival or recurrence-free survival of the patients suffering from a SCC in the oral cavity or oropharynx. Our observations suggest that the function of wild-type p53 to induce apoptosis is lost in at least half of the SCCs under study and that the physiological function of bcl-2 as potent inhibitor of apoptosis is widely preserved in oral SCC. Received: 27 April 1999 / Accepted: 31 August 1999     

Standardized AgNOR analysis of the invasive tumour front in oral squamous cell carcinomas

In the last decade, silver staining of nucleolar organizer region-associated proteins (AgNORs) has been widely used in tumour pathology both for diagnostic and for prognostic purposes. However, a reliable and reproducible assessment of these proteins on routinely processed archival tissues has only become possible since the recent introduction of standardized staining method and computer-aided morphometric analysis. In the present study, the AgNOR content at the invasive front of 80 squamous cell carcinomas of the floor of the mouth/tongue was investigated using this novel approach, with regard to prognosis and a variety of clinico-pathological parameters. All standardized AgNOR parameters [mean of AgNOR number, mean of AgNOR area, coefficients of variation (CV) of both AgNOR number and area] were statistically significantly associated with the clinical course. The strongest correlation was found for the AgNOR-area univariate analysis (P=0·006). In multivariate analysis, the mean of AgNOR number could independently predict both overall (P=0·01) and disease-free survival (P=0·001). It is concluded that standardized staining and computer-aided analysis of AgNORs are prerequisites for an objective and reproducible AgNOR assessment, which has potential as a supplementary diagnostic and prognostic tool in oral cancer. © 1997 John Wiley & Sons, Ltd.     

Thymidine phosphorylase expression results in a decrease in apoptosis and increase in intratumoral microvessel density in human gastric carcinomas

Thymidine phosphorylase (dThdPase) / platelet- derived endothelial cell growth factor (PD-ECGF) is expressed at higher levels in a variety of human carcinomas than in adjacent normal tissue. The higher expression is associated with an increase in intratumoral microvessel density (IMVD) and an unfavorable patient prognosis. This study examined the role of dThdPase in apoptosis, IMVD and p53 expression in human gastric carcinomas. dThdPase expression was noted in 12 (35.3%) of 34 early carcinomas, and in 20 (55.6%) of 36 advanced carcinomas. At least 10 areas consisting of carcinoma cells with diffuse dThdPase expression from the 32 dThdPase-positive tumors (category I), and 10 areas without dThdPase expression from the 38 negative tumors (category II) were selected from each case. For early gastric carcinoma, the mean IMVD was 88.8±19.4 in category I and 61.4±17.3 in category II carcinomas, while for advanced gastric carcinoma, the mean IMVD was 98.8±21.0 in category I and 76.0±27.1 in category II carcinomas. The mean IMVD was significantly higher in category I than in category II tumors (P<0.05). The mean apoptotic index (AI: percentage of apoptotic cells) was 1.95±1.30 in category I, and 3.76±1.49 in category II carcinomas for early gastric carcinoma, and 1.51±0.98 in category I and 2.14±0.66 in category II carcinomas for advanced gastric carcinoma, the value of the mean AI being significantly (P<0.05) higher in dThdPase- negative tumors (category II) than in the positive tu-mors (category I), regardless of tumor stage or histological type. There was a significant inverse correlation (P<0.001) between AI and IMVD. These results indicate that dThdPase expression is associated with both an increase in intratumoral microvessels and a decrease in apoptosis in human gastric carcinomas. Received: 8 November 1999 / Accepted: 20 January 2000     

Prognostic significance of CD9 expression in locally advanced gastric cancer treated with surgery and adjuvant chemoradiotherapy

The tetraspanin transmembrane protein CD9 plays an important role in inhibiting cell motility in numerous neoplastic cell lines, including lung, gastric, pancreatic, and bladder carcinomas. The prognostic importance of CD9 in the survival of gastric carcinoma patients has not been examined to date, and in the present study, we attempted to define its prognostic value. The study included 49 (35 men and 14 women) patients with locally advanced (stages II–IV) gastric cancer. The median age was 55 years (range, 22–73 years). Surgery was the initial treatment for all patients, followed by adjuvant chemoradiotherapy. Tissue sections were evaluated immunohistochemically with a monoclonal anti-CD9 antibody. Of the 49 patients with gastric adenocarcinoma, 11 (22.4%) were CD9-positive, and 38 (77.6%) were CD9-negative. A significant prognostic value in disease-free survival and overall survival was observed in T classification and CD9 positivity. In conclusion, CD9 expression in gastric cancer appears to be associated with poor prognosis.     

Prognostic significance of p53 gene mutations and p53 protein expression in synovial sarcomas

Alterations to p53 seem to be of prognostic significance in soft tissue sarcomas, but their significance for synovial sarcomas has not been studied. We analysed 34 synovial sarcomas in 19 patients for p53 alterations (p53 gene mutations + p53 immunopositivity) and examined this factor for its prognostic value in a group of 15 primary tumours. DNA was prepared from paraffin-embedded tumour material by a modified proteinase K/phenol/chloroform extraction. p53 gene mutations of exons 5–8 were analysed by the PCR-SSCP-sequencing method. p53 protein expression was evaluated by immunohistochemistry using the murine monoclonal antibody DO1. We found two missense mutations (5.9%) and ten p53 immunopositive cases (29.4%). Both tumours with p53 mutations showed p53 protein expression. There was no significant correlation between p53 alteration and histological subtype, age, sex, or tumour size. The 5-year survival rate was 24.1%. Overall survival was significantly reduced in patients having synovial sarcomas with p53 alterations (P<0.001). In the multivariate Cox’s analysis, only p53 alterations (P=0.032) and tumour size (P=0.023) emerged as independent prognostic factors. We suggest that p53 alterations may be a useful prognostic indicator in synovial sarcomas, allowing rational clinical treatment and follow-up. Received: 13 April 1999 / Accepted:18 May 1999     

Morphogenesis of nonpolypoid colorectal adenomas and early carcinomas assessed by cell proliferation and apoptosis

Nonpolypoid neoplasms, as well as ordinary polypoid tumours, are occasionally found in the colorectum. To clarify whether cell kinetic status affects the macroscopic morphology of colorectal neoplasms, we investigated proliferative indices (PI), apoptotic indices (AI), and the expression of apoptosis-related gene products. We examined 110 colorectal neoplasms comprised of 36 polypoid, 38 flat elevated and 36 depressed tumours. According to WHO’s criteria these tumours consisted of 61 adenomas with low grade dysplasia (LGD), 30 adenomas with high grade dysplasia (HGD) and 19 carcinomas with submucosal invasion. Apoptotic cells were detected by TUNEL staining. Proliferating cells and apoptosis-related gene products were assessed by immunohistochemistry for Ki-67, p53, Bcl-2, and Bax antigens. AI were closely associated with macroscopic morphology in adenomas but not in carcinomas. PI were relatively constant among the three macroscopic types in adenomas and carcinomas. Median AI values of polypoid, flat elevated and depressed tumours were 1.8%, 2.1% and 4.6% for adenomas with LGD, 0.8%, 2.4% and 6.2% for adenomas with HGD and 2.9%, 4.0% and 3.6% for carcinomas, respectively. Overall PI were significantly higher in carcinomas than in adenomas with LGD, whereas AI were not different. Although the incidence of expression was significantly higher in carcinomas for p53 and in adenomas for Bcl-2 than the others, the expression of apoptosis-related gene products (p53, Bcl-2 and Bax) was similar among polypoid, flat elevated and depressed tumours. Macroscopic morphology of colorectal adenomas is determined by the apoptosis not by proliferation, and high apoptosis found in depressed adenomas implies their low net growth. Received: 1 July 1999 / Accepted: 17 January 2000     

Biological and prognostic significance of stratified epithelial cytokeratins in infiltrating ductal breast carcinomas

 The biological significance of the differential expression of cytokeratin (CK) polypeptides in breast carcinomas is unclear. We examined the CK profiles of 101 primary infiltrating ductal breast carcinomas using monoclonal antibodies directed against 11 different CKs and against vimentin. Two major CK phenotypes were distinguished: first, a phenotype expressing only the simple-epithelial CKs 7 (variably), 8, 18 and 19, and secondly, a bimodal phenotype co-expressing significant amounts of one or more of the stratified-epithelial CKs 4, 14 and 17. The vast majority of G1 and G2 carcinomas had the simple-epithelium phenotype, as did a subgroup of G3 carcinomas. Interestingly, the majority (62%) of G3 carcinomas exhibited the bimodal phenotype, with the expression of CKs 4, 14 and 17 being statistically correlated with poor histological differentiation and absence of steroid hormone receptors. The distribution of vimentin only partially overlapped with that of these stratified-epithelial CKs. Prognostic analyses suggested that the presence of CKs 4, 14 and/or 17 was associated with short overall and disease-free survival in subgroups comprising G3, oestrogen-receptor-negative and vimentin-negative tumours. In node-positive tumours the correlation between these CKs and a shorter disease-free interval attained statistical significance (log rank, 0.0096). Thus, abnormal CK profiles in ductal breast carcinomas appear to reflect disturbed regulation of differentiation-related gene expression programmes and may prove to be of clinical value. Received: 26 August 1997 / Accepted: 11 February 1998     

c─erbB─2、AgNOR在乳腺癌中的预后价值及其相互关系探讨

对８８例乳腺癌作了ＡｇＮＯＲ银染计数及ｃ─ｅｒｂＢ─２癌蛋白的免疫组化研究。结果发现ｃ─ｅｒｂＢ─２阳性者，病死率大于ｃ─ｅｒｂＢ─２阴性者（Ｐ＜０．０１）；ＡｇＮＯＲ计数＞５者，病死率大于ＡｇＮｏＲ≤５者（Ｐ＜０．０１），表明了这两个指标对预后具有明显的价值。同时发现ＡｇＮＯＲ值＞４者，ｃ─ｅｒｂＢ─２阳性率显著高于ＡｇＮＯＲ≤４者（Ｐ＜０．０５），表明这两个指标之间也有一定的关系。我们还发现ｃ─ｅｒｂＢ─２阳性、ＡｇＮＯＲ值＞５者，病死率显著大于ｃ─ｅｒｂＢ─２阴性、ＡｇＮＯＲ值≤５者组。     

Analysis of hyperplastic foci in livers with hepatocellular carcinomas by flow cytometry and AgNOR staining

The phase S ratlo in cell cycles were analyzed in livers with hyperplastic foci (HPF) and in livers without HPF by nuclear DNA determinatlons using flow cytometry, and by stalning wlth argyrophilic protelns of the nucieolar organlzer reglon (AgNOR). Flow cytometric analysis was done on 50 fresh frozen speclmens of livers resected from 50 patients wlth hepatocellular carcinoma (HCC). Paraffin sections from the same patients were analyzed uslng AgNOR staining. There were 25 cases each wlth and without HPF. We examined the stage of fibrosis and the grade of inflammatory activity according to the modlfied Scheuer and Desmet scale. The incidence of HCC recurrence among these patlents was also studied. The average phase S ratio of the livers of the patients with HPF was 6.5+3.2%, and that of the livers of the patients without HPF was 4.0±2.5%. The ratio differed slgnificantly between the two groups (P<0.01). The average AgNOR score for HPF lesions of the HPF-positlve cases was 1.6020.34, that for non-HPF lesions In the HPF-positive cases was 1.2920.12, and that for the HPF-negative cases was 1.1920.14. Significant differences were found between the average AgNOR scores for HPF lesions of the HPF-posltive cases and the non-HPF lesions of the HPF-posltive cases (P<0.0l), as well as between the non-HPF lesions in the HPF-positive cases and the HPF-negatlve cases (P-cO.05). Severe fibrosis (stage 3) and cirrhosls (stage 4) were found In 76% of HPF-positive cases and 48% of HPF-negatlve cases. The llvers of HPF-posltlve patlents were slgnificantiy more cirrhotic than those of HPF-negative patients (R0.05). The association between HPF and the Inflammatory grade was not slgnlficant (Ao.05). The incldence of HCC recurrence among HPF-positive cases was significantly higher than that among the HPF-negative cases (P<0.05). The average phase S ratio of the recurrent HPF-positive patients was 7.48+3.48%, slgnlficantly higher than that of HPF negative cases (5.57*3.06%, Pc0.05). Hyperplastic foci of the llver was shown to be a hlghly prollferatlve lesion. The proliferative activity of the non-HPF lesions in the HPF-positive patients was also higher than that of the HPF-negative patients. Hyperplastic focl tended to be present in cirrhotic livers, but it was not associated wlth the grade of inflammatory activlty of the Iiver. Hyperplastic focl may represent an important predictor of recurrence after hepatic resection.     

Shh和Ptch在胃癌中的表达及其临床意义

目的检测Shh、Ptch在胃癌中的表达,分析其与临床病理特征的关系,探讨二者在胃癌发生发展的作用。方法采用免疫组化法检测116例胃癌、50例正常胃粘膜中Shh、Ptch的表达。结果 Shh和Ptch在胃癌中高表达,且与肿瘤直径、浸润深度、分化程度、淋巴结转移及预后相关(P<0.05)。二者表达呈正相关。结论 Shh和Ptch的表达上调可能与胃癌的发生发展有关,并起协同作用。     

Intestinalization of gastric signet ring cell carcinomas with progression

 Recent developments in mucin histochemistry and immunohistochemistry have made reliable determination of the gastric and intestinal phenotypes of gastric carcinoma cells possible. Phenotypic expression changes from gastric epithelial cell type to intestinal epithelial cell type with the growth of gastric tumours in experimental animals. We studied cell differentiation in gastric signet ring cell carcinomas with progression in 203 surgically obtained specimens. The results showed that the proportion of gastric phenotype carcinomas, in which over 90% of the tissue consists of gastric epithelial cell type cells, decreases with the depth of invasion. The proportion of mixed phenotype carcinomas (between 10% and 90% of the tissue made up of gastric and/or intestinal epithelial cell type cells) increases. The intestinal phenotype (over 90% intestinal epithelial cell type carcinoma cells) was found in four carcinomas (about 2%) involving the serosa. No clear relationship was evident between phenotypic expression of carcinoma cells and the degree of intestinal metaplasia of the surrounding mucosa. Progression of gastric signet ring cell carcinomas is associated with a phenotypic shift from gastric to intestinal type expression. Received: 7 January 1997 / Accepted: 12 March 1997     

Regulation of proliferation and apoptosis in sporadic and hereditary medullary thyroid carcinomas and their putative precursor lesions

C-cell hyperplasia (CCH) and medullary thyroid carcinoma (MTC) in patients affected by germline mutations of the RET oncogene represent an exceptional opportunity to study the regulation of proliferation and apoptosis during tumour initiation and progression. In 56 specimens [CCH, n=1; MTC with CCH, n=26; MTC, n=20; lymph-node metastasis (LNM), n=9] from 46 patients [multiple endocrine neoplasia type 2a (MEN2a), n=24; MEN2b, n=2; familiar MTC (FMTC), n=4; sporadic MTC, n=16] and 3 cases of non-neoplastic CCH, proliferation activity (MIB1), the rate of apoptosis [dUTP nick end labelling (TUNEL)] and expression of p53, bcl-2, bcl-x and bax were investigated and compared with clinical data. In MEN-associated CCH and small MTC, bcl-2 was strongly expressed, bcl-x was moderately expressed and bax was only weakly expressed. Advanced tumours and LNM did show a more heterogeneous bcl-2 staining accompanied by an increased bax expression and accelerated proliferation. The rate of apoptosis was extremely low in all investigated tumours. P53 was detectable in three patients with rapidly growing and extensively metastasising MTC. No somatic p53 mutations were found. Hereditary MTC with germline RET mutations at codon 918 (MEN2b) and codon 634 revealed a bias towards a higher proliferation activity at a younger age and are more frequently accompanied by LNM. CCH and MTC are characterised with a preponderance of bcl-2 as a factor blocking the programmed cell death. While MTC, in general, is a slowly growing tumour, a minority of tumours do progress rapidly with high proliferation. The factors leading to an accelerated tumour progression do not seem to take their effect via the regulation of apoptosis. Certain alterations of RET are supposed to have a direct or indirect implication on proliferation and, because of this, an effect on the clinical course. Received: 10 January 2000 / Accepted: 1 March 2000     

Proliferation marker Ki-S11 – a prognostic indicator for squamous cell carcinoma of the hypopharynx

As a potential prognostic factor, the proliferative activity of 131 squamous cell carcinomas (SCC) of the hypopharynx and 47 of their cervical lymph-node metastases was analyzed retrospectively by means of monoclonal antibody Ki-S11 immunostaining, which specifically detects the Ki-67 antigen on paraffin-embedded tissue. Median follow-up time was 37.6 months. Ki-S11 revealed distinctive patterns of proliferating cells related to the degree of differentiation. The proliferation fractions in the primaries and their lymph-node metastases did not differ significantly. Patients with high proliferating hypopharynx carcinomas (>45% labeled cells) had a significantly lower 5-year-survival rate (16%) than patients with low proliferating tumors, whose 5-year-survival rate was 30% (P=0.01). A statistically significant positive correlation was also observed between proliferative activity and lymph-node status (P=0.012). In conclusion, the proliferative activity as determined by means of Ki-S11 immunostaining is of prognostic value with respect to both survival and metastatic risk in SCC of the hypopharynx. Received: 6 May 1999 / Accepted: 15 July 1999     

Downregulated parafibromin expression is a promising marker for pathogenesis, invasion, metastasis and prognosis of gastric carcinomas

Parafibromin is a protein encoded by the hyperparathyroidism 2 oncosuppressor gene and its downregulated expression is involved in pathogenesis of parathyroid carcinomas. To clarify the roles of parafibromin expression in tumourigenesis and progression of gastric carcinomas, it was examined by immunohistochemistry (IHC) on tissue microarray containing gastric carcinomas (n = 508), adenomas (n = 45) and gastritis (n = 49) with a comparison of its expression with clinicopathological parametres of carcinomas. Gastric carcinoma cell lines (MKN28, AGS, MKN45, KATO-III and HGC-27) were studied for parafibromin expression by IHC and western blot. Parafibromin expression was localised in the nucleus of gastric epithelial cells, adenoma, carcinoma cells and cell lines. Its expression was gradually decreased from gastritis to gastric carcinoma, through gastric adenomas (p < 0.05) and inversely correlated with tumour size, depth of invasion, lymphatic invasion, lymph node metastasis and Union Internationale Contre le Cancer (UICC) staging (p < 0.05) but not with sex or venous invasion (p > 0.05). Parafibromin was strongly expressed in older carcinoma patients compared with younger ones (p < 0.05). There was stronger positivity of parafibromin in intestinal-type than diffuse-type carcinomas (p < 0.05). Univariate analysis indicated cumulative survival rate of patients with positive parafibromin expression to be higher than without its expression (p < 0.05). Multivariate analysis showed that age, tumour size, depth of invasion, lymphatic invasion, lymph node metastasis, UICC staging and Lauren’s classification but not sex, venous invasion or parafibromin expression were independent prognostic factors for carcinomas(p < 0.05). Downregulated parafibromin expression possibly contributed to pathogenesis, growth, invasion and metastasis of gastric carcinomas. It was considered as a promising marker to indicate the aggressive behaviours and prognosis of gastric carcinomas.     

乳腺癌中AgNOR和NDPK／nm23的预后价值及相互关系

目的：研究ＡｇＮＯＲ和ＮＤＰＫ／ｎｍ２３与乳腺癌预后的关系。方法：对５２例乳腺癌作ＡｇＮＯＲ计数及ＮＤＰＫ／ｎｍ２３免疫组化染色。结果：ＡｇＮＯＲ〈４者，５年生存率显著高于ＡｇＮＯＲ≥者。ＮＤＰＫ／ｎｍ２３阳性者。５年生存率显著高于ＮＤＰＫ／ｎｍ２３阴性者。ＡｇＮＯＲ〈４、ＮＤＰＫ／ｎｍ２３阳性者，５年生存率高于ＡｇＮＯＲ≥４、ＮＤＰＫ／ｎｍ２３阳性者。ＡｇＮＯＲ≥４者，ＮＫＰＫ／ＮＭ２３阴性者。     

Expression of MUC1 and MUC2 mucins in gastric carcinomas: their relationship with clinicopathologic parameters and prognosis

The aim of this study was to investigate the relationship between MUC1 and MUC2 mucin expressions and clinicopathologic variables in gastric carcinomas with regard to survival times. MUC1 and MUC2 expressions were revealed immunohistochemically in 143 gastric carcinomas. Of these 143 patients, follow-up data were available for 45 (median survival time of 30 months, ranging from 2 to 80 months). MUC1 was detected in 82 (58%), and MUC2 in 60 (42%) out of 143 cases. Papillary adenocarcinomas showed significantly higher MUC1 and MUC2 immunoreactivity than did signet-ring cell and mucinous tumors (p = 0.045 and p = 0.01, respectively). MUC1 was highly positive in intestinal-type carcinomas (p = 0.006), whereas intestinal and diffuse carcinomas did not differ in MUC2 expression. There was a positive correlation between tumor differentiation and MUC1 expression. However, no correlation was found between MUC1 and MUC2 expressions and angiolymphatic invasion. According to the TNM classification, stage 1A tumors have significantly lower rates of MUC1 reactivity compared to higher stages (p = 0.04). The patients with gastric carcinomas expressing MUC1 showed significantly poorer survival than those without MUC1 expression (p = 0.04). The present study suggests that MUC1 expression be a useful prognostic factor for predicting the outcome of gastric carcinoma patients, whereas the role of MUC2 expression is still unclear.     

Immunohistochemical analysis of apoptosis-inducing factor (AIF) expression in gastric carcinomas

Mounting evidence suggests that both survival and death of cells play an important role in tumorigenesis. Apoptosis-inducing factor (AIF), a mitochondrial protein, plays an important role in the caspase-independent apoptosis. Also, recent studies have demonstrated that AIF has an oxidoreductase function that confers survival on the cells. As the roles of AIF in cancers are largely unknown, it may be important to identify the expression pattern of AIF in cancer tissues. In this study, which aims at defining the role of AIF in gastric tumorigenesis, we analyzed the expression of AIF in 60 gastric adenocarcinomas using immunohistochemistry. AIF expression was detected in the cytoplasm in 42 cases (70%) of gastric carcinoma. We also analyzed AIF expression in early (EGC) and advanced gastric carcinomas (AGC). AIF was expressed in 25 (73%) of 34 intestinal-type cancers and in 17 (65%) of 26 diffuse-type cancers. However, there was no significant difference in AIF expression with respect to the histological subtypes or the depth of invasions, either. In normal gastric mucosal cells, parietal cells, but not other mucosal cells, expressed AIF. Increased expression of AIF in malignant gastric epithelial cells compared to the normal mucosal cells suggests that AIF expression may play a role in gastric tumorigenesis. Also, the data suggest that AIF expression may play a role in the function of the gastric parietal cells.