Positive Rate Of Ki-67 Research Articles

Analysis of the immunohistochemical subtypes and prognosis of primary diffuse large B cell lymphoma of the central nervous system

To analyze the subtypes of primary diffuse large B cell lymphoma of the central nervous system (CNS DLBCL) and to explore the relationship between the subtype classification and prognosis. Immunohistochemical staining was used to determine the expression of CD20, CD3, CD10, Bcl-6, Mum-1, CD5, Bcl-2, Ki-67, FOXP-1, GCET-1, BLIMP-1 and LMO-2 antigens on paraffin-embedded sections of 47 cases. Hans, Choi and Tally subtypes were classified, and univariate and multivariate analyses were used to elucidate the relationship between the subtypes and prognosis. In the 47 cases, the expression of Bcl-2 in the tumor cells was 46.8%, CD10 4.3%, Bcl-6 70.2%, Mum-1 53.2%, GCET-1 36.2%, BLIMP-1 4.3%, FOXP-1 63.8% and LMO-2 19.2%. The positive rate of Ki-67 was 30% to 95%, with a median of 80%, of which 12 cases (25.5%) was > or = 90%. The Hans subtype classification showed 16 cases (34.0%) were of GCB type and 31 cases (66.0%) of non-GCB type. The Choi subtype classification showed 16 cases (34.0%) were of GCB type and 31 cases (66.0%) of ABC type. The Tally subtype classification showed 6 cases (12.8%) were of GCB type and 41 cases (87.2%) of non-GCB type. The results of this study show that there is no significant correlation between the three subtypes and prognosis. The prognosis is correated with post-operative radiotherapy, chemotherapy and MTX therapy.

Inhibitory effects of thymoquinone on human pancreatic carcinoma orthotopically implanted in nude mice

To explore the anti-neoplastic and anti-metastatic effects of thymoquinone on the model of human pancreatic carcinoma established by surgical orthotopic implantation (SOI) in nude mice. After a 3-week implantation, 40 mice were randomized into 4 groups: control group, feed with 1% ethanol; low-dose thymoquinone group (L-TQ 5 mg/kg BW daily by i.g.), high-dose thymoquinone group (H-TQ 20 mg/kg BW daily by i.g.) and gemcitabine group (GEM 100 mg/kg BW twice a week by i.p.) (n = 10 each). All treatment sessions lasted for 2 weeks. At Week 8 post-implantation, tumor weight, inhibition rate and the presence of metastasis were evaluated respectively after sacrificing. Immunohistochemistry was used to detect the positive expressions of Ki-67, XIAP (X-linked inhibitor of apoptosis protein) and MMP-9 (matrix metalloproteinase 9) in tumors. The tumor growth-inhibiting rates of L-TQ group, H-TQ group and GEM group were 42.57%, 64.11% and 54.77% respectively. The rates of metastasis in L-TQ group and H-TQ group were 60% and 50% versus GEM group (100%). And the differences had statistical significance (P < 0.05). The positive rates of Ki-67 in group L-TQ and group H-TQ were 37% ± 3% and 32% ± 2% versus group GEM (55% ± 4%). And the differences had statistical significance (P < 0.05). The positive rates of XIAP in group L-TQ and group H-TQ were 30% ± 3% and 28% ± 5% versus group GEM (56% ± 4%). And the differences had statistical significance (P < 0.05). The positive rates of MMP-9 in group L-TQ and group H-TQ were 57% ± 7% and 53% ± 2% versus group GEM (73% ± 4%). And the differences had statistical significance (P < 0.05). Thymoquinone has the anti-neoplastic and anti-metastatic effects on the human pancreatic carcinoma in nude mice. And the above effects may be correlated with the down-regulated expressions of XIAP and MMP-9.

Expressions of Ki-67 and p53 in pulmonary sclerosing hemangioma and the clinical significance

Objective To study the expressions of Ki-67 and p53 in the surface cells and polygonal cells in pulmonary sclerosing hemangioma (PSH) and investigate the relation of cell proliferation index and biological behaviour of the tumor. Methods Double-staining immunohistochemistry was used to detect the expressions of Ki-67 and CK8/18 protein. Double immunofluorescence staining was used to detect the expressions of p53 and AE1/AE3 protein. Results The positive signal of AE1/AE3 and CK8/18 were localized in cytomembrane of surface cells. The positive signal of Ki-67 and p53 were localized in cell nucleus of the two kinds of cells. The positive rate of Ki-67 was under 1％ in surface cells and 1％-10 ％ in polygonal cells. p53 protein was mainly expressed in polygonal cells (6/9, 33.3 ％) and only exsited in seldom surface cells. Conclusion There are differences on cellular morphous and immunophenotype between the surface cells and polygonal cells. The proliferation index and gene mutation are all predominant in polygonal cells than in surface cells. The biological behaviour of PSH maybe mainly be decided by the polygonal cells. Key words: Pulmonary sclerosing hemangioma; Fluorescent antibody technique; Biological behaviour; AE1/AE3; p53; Ki-67

Effect of LRIG3 gene overexpression on proliferation of glioma U251 and U87 cells and expression of PCNA and Ki-67

Objective To explore the effect of overexpression of LRIG3 gene on proliferation of glioma cells and expression of proliferating cell nuclear antigen (PCNA) and Ki-67, and the possible mechanisms. Methods The plasmid containing LRIG3 gene and control was transduced into glioma U251 and U87 cells respectively. The mRNA and protein levels of LRIG3 were detected by using reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. Cell proliferation was examined by methyl thiazol tetrazolium (MTT) assay. The expression of PCNA and Ki-67 was detected by strept avidinbiotin complex (SABC). Results Compared with control cells, the mRNA levels of LRIG3 were raised by 67.6％ and 79.9％ in LRIG3 cells of U87 and U251, respectively, and the protein levels were increased by 62. 3％ (U87) and 91.0％ ( U251 ) respectively. Overexpression of LRIG3 resulted in the reduction of cell proliferation. The positive rate of PCNA was significantly lower in LRIG3 cells than in control cells [U87: (33.60±4.82)％ vs (55.50±4.01)％; U251: (27.49±3.17)％ vs (47.81 ±4.67)％ (P＜0. 05)]. The positive rate of Ki-67 was also significantly decreased in LRIG3 transduced cells as compared with control cells[U87 : (23. 50 ±4. 60)％ vs (55.20 ±4. 19)％ ; U251 : (24. 30 ± 3. 76) ％ vs (48. 50 ± 6. 11 ) ％ ( P ＜ 0. 01 )]. Conclusion Up-regulating LRIG3 gene expression can reduce the proliferation of glioma U87 and U251 cells. Key words: Glioma; LRIG3 ; Proliferating cell nuclear antigen; Ki-67

Association of PML Expression with Chemotherapy-Resistance In Multiple Myeloma Cells

AbstractAbstract 2959 Background:Although several novel agents have improved the prognosis of patients with multiple myeloma (MM), it still remains an incurable disease because of the difficulty to eradicate MM cells by current therapeutic approaches. Recent studies have revealed that a subset of malignant cells, cancer stem cells, contribute to chemotherapy-resistance in cancer treatment. Promyelocytic leukemia gene product (PML), known as a tumor suppressor through a variety of cellular functions in a nuclear macromolecular structure called the PML nuclear body, has been reported to be responsible for the chemotherapy-resistance by regulating cell cycle in chronic myeloid leukemia. We therefore investigated the impact of PML expression on the cellular proliferation status of MM cells and patients' prognoses. Materials/Methods:Bone marrow clot sections from 48 patients with newly diagnosed MM from Jan 1998 to Dec 2009 before any therapy at diagnosis were obtained, and analyzed, according to appropriate procedure approved by IRB at the Tokai University School of Medicine (Kanagawa, Japan) with written informed consent. They were doubly-stained with a combination of anti-PML/anti-CD138 and anti-Ki67/anti-CD138. For evaluation of the relation between PML status and cellular proliferation, the positive rates of PML and Ki67 in CD138 positive cells were compared. For investigation of the impact of PML expression on the prognosis of MM, the patients were divided into 3 groups, according to the PML positive rates in the CD138 positive cells: negative/low (less than 25 percentile: 12 cases), intermediate (from 25 to 75 percentile: 24 cases) and high (more than 75 percentile: 12 cases). Their overall survivals were compared using log-rank test. Furthermore, the PML positive rates between before and after treatments were compared using paired t-test. Results:The median observation period of 48 cases was 915 days. The median age of the patients was 62.5 (38-76) at diagnosis. All the patients were underwent combination chemotherapies containing alkylating agents as initial therapies. Two and nine patients were underwent allogeneic and autologous stem cell transplantation during the clinical courses, respectively. The numbers of patients of international staging system (ISS) stage I, II and III were 17, 14 and 17 cases. The PML positive rates in each case ranged from 0% to 83.8%. They were not correlated with ISS stages (Spearman r = 0.083) and the Ki67 positive rates (Spearman r = -0.13). The PML positive rates in the negative/low, intermediate and the high groups were less than 22.1%, from 22.1 to 56.6% and more than 56.6%, respectively. No significant difference in overall survival was observed among the 3 groups (p>0.05). However, there were significant differences in two year survival rate when the 3 groups were compared (100%, 85.2% and 54.7%; p=0.015) (Fig. 1). In 13 patients whose bone marrow clot sections were sequentially collected, the PML positive rates after treatments were significantly higher than those at diagnosis (p=0.0042) (Fig. 2). Especially, PML positive rates in all the 3 patients from the negative/low group were progressively increased (0.3 to 82.6%, 14.1 to 100%, 19.0 to 37.5%), and 2 of them died due to disease progression. On the other hand, 2 patients whose PML positive rates decreased after treatment were alive more than 5 years without therapies. Conclusion:Our data indicated that the level of the PML expression at diagnosis was a possible prognostic factor for early course of the disease (2 years after diagnosis). Chemotherapies might induce PML expression in MM cells or select PML positive MM cells. These findings suggest that PML expression presumably reflect chemotherapy-resistance in MM cells. The molecular mechanism of the association is now under investigation. [Display omitted] [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Nuclear expression of nerve growth factor in meningioma and its clinical significance

Objective To investigate the expression of nerve growth factor (NGF) in meningioma and its biological significance. Methods Fifty-six cases of meningioma sections were immunohistochemi-cally stained with NGF, PR, Ki67 antibodies. Corresponding patients were followed up for recurrence of meningioma. Results NGF nuclear positive rate (41. 1% ) was higher than Ki67 positive rate (35. 7% ) (P>0.05 ). PR positive rate was 60. 7%. NGF nuclear positive rate was positively correlated with Ki67 positive rate (r =0. 741 ,P<0. 01), while negatively with PR positive rate (r = -0. 59,P<0.01). The median relapse time of NGF nuclear positive patients was 36. 000 ± 2. 484 months, which was significantly shorter than that of NGF nuclear negative group (59.000 ± 2. 295 months) (P <0.01 ). Conclusion NGF nuclear positive rate can be used as an indicator for proliferation and prognosis of meningioma. Key words: Meningioma; Nerve growth factor; Prognosis

The expression of CK20 and Ki-67 in bladder cancer

Objective To investigate the correlation of CK20 and Ki-67 expression in tumor to metastasis, invasion, and prognosis of bladder cancer. Methods The expression of CK20 and Ki-67 in 154 specimens of bladder cancer was detected by SP immunohistochemistry. Results Positive rate of CK20 was 66. 9% in bladder cancer tissues. CK20 staining in cancer tissue was positively related with T stage and distant metastasis (P<0.05). Positive rate of Ki-67 was 81.8% in bladder cancer tissues. Ki-67 staining in cancer tissue was positively related with pathologic grade and T stage and distant metastasis (P < 0.05). Spearman' s rank correlation had showed both correlations (P < 0. 05). Conclusion CK20 and Ki-67 maybe participate in invasion and metastasis of bladder cancer. CK20 and Ki-67 may be an prognostic factor and when used in combination with pathologic grading and clinical staging, may increase accuracy of predicting prognosis of patients with bladder cancer. Key words: CK20; Ki-67; Bladder-cancer/ oncology; Diagnosis; Gene expression

Analysis of cell cycle-related proteins in gastric intramucosal differentiated-type cancers based on mucin phenotypes: a novel hypothesis of early gastric carcinogenesis based on mucin phenotype

BackgroundAbnormalities of cell cycle regulators are common features in human cancers, and several of these factors are associated with the early development of gastric cancers. However, recent studies have shown that gastric cancer tumorigenesis was characterized by mucin expression. Thus, expression patterns of cell cycle-related proteins were investigated in the early phase of differentiated-type gastric cancers to ascertain any mechanistic relationships with mucin phenotypes.MethodsImmunostaining for Cyclins D1, A, E, and p21, p27, p53 and β-catenin was used to examine impairments of the cell cycle in 190 gastric intramucosal differentiated-type cancers. Mucin phenotypes were determined by the expressions of MUC5AC, MUC6, MUC2 and CD10. A Ki-67 positive rate (PR) was also examined.ResultsOverexpressions of p53, cyclin D1 and cyclin A were significantly more frequent in a gastric phenotype than an intestinal phenotype. Cyclin A was overexpressed in a mixed phenotype compared with an intestinal phenotype, while p27 overexpression was more frequent in an intestinal phenotype than in a mixed phenotype. Reduction of p21 was a common feature of the gastric intramucosal differentiated-type cancers examined.ConclusionsOur results suggest that the levels of some cell cycle regulators appear to be associated with mucin phenotypes of early gastric differentiated-type cancers.

Regulation of NF-κB in neural stem cell proliferation

Obiective To explore the role of nuclear factor-κB(NF-κB)in neural stem cells (NSCs)proliferation.Methods Neurospheres got from primary culture and subculture and identified by nesfin.were ased in the following studies.NSCs were divided randomly into 3 groups:control group,TNF-αgroup and PDTC group.In control group.NSCs were cultured in NSCs media routinely.In TNF-α group,the cells were cultured in NSCs media containing 10 μg/L TNF-α.NSCs in PDTC group were treated with NSCs media containing 0.1 retool/L PDTC.The NSCs in each group were sampled at 0.5.4.72 h post.stimulalion.respectively. The activity of NF-κB was detected by immunofluorescenee staining and Western blotting.Immunofluorescence staining was also emploved to detect the expression of Cyclin D1 and Ki-67.the wellcharacterized proliferation markers.Results Immunofluoreseenee staining of nestin indicated that most cells in the neurospheres expressed nestin positively.Immunofluorescence staining and Western blotting resuits showed that NF-κB/p65 subunit was transloeated into the nuclear,suggesting the NF-κB pathway was activated in TNF stimulated NSCs.The positive rate of Cychn Dl in TNF-α group and control group was (6S.6±4.2)%and(38.8±3.7)%,respectively,both higher than in PDTc group significantly[(24.2±2.8)%,P＜0.01].The positive rate of Ki-67 in TNF-α group and control group was(48.2±3.6)%and (35.2±4.7)%,respectively,both higher than in PDTC group significantly[(18.7±1.8)%,P＜0.01].Conclusion The activation of NF-κB might promote the proliferation of NSCs and vice versa.NF-κB might play an imporiant role in NSCs proliferation. Key words: Nuclear factor-κB; Neural stem cells; Tumor necrosis factor; Proliferation

Prognostic indicators of malignancy in adrenal pheochromocytomas: clinical, histopathologic, and cell cycle/apoptosis gene expression analysis

Pheochromocytomas are malignant in approximately 10% of patients. The histologic differentiation between benign and malignant tumors is difficult, the latter diagnosed by the presence of metastatic disease or recurrence. To determine if postoperative histologic evaluation using the previously proposed Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) and cell cycle/apoptosis markers can predict patients at risk for recurrence. Using the Memorial Sloan-Kettering Cancer Center adrenal database, we identified 48 patients with 51 resected pheochromocytomas (1987-2006). A senior endocrine pathologist, blinded to clinical outcome, reviewed the histopathologic characteristics of all cases using the PASS system. This pheochromocytoma scoring system is based on the presence of 12 different histologic parameters, including tumor necrosis, mitotic rate, tumor cell spindling, and the presence of large cell nests. In addition, we constructed a tissue microarray of all 5 malignant tumors and 41 of the benign tumors. By immunostaining of the tissue microarray, we assessed the expression of 7 different cell cycle/apoptosis-related genes (p53, Ki-67, Bcl-2, mdm-2, cyclin D1, p21, and p27). Forty-three patients had a benign clinical course while 5 patients harbored a clinically malignant pheochromocytoma. Tumor necrosis (focal or confluent) was a particularly powerful indicator of malignancy present in 4 of 5 patients (80%) with malignant tumors, but only in 3 of 42 cases (7%) with benign neoplasms (P = .0009). The presence of a high mitotic rate (>3/10 high power fields) and tumor cell spindling significantly correlated with malignancy (P = .026 and .041, respectively). High cellularity was more often present in the malignant lesions (P = .050). There was a highly significant difference in PASS scores between benign and malignant cases (P = .0003). All malignant pheochromocytomas had a PASS score >/=6, well above the previously proposed >/=4 cutoff value. Two of the 4 patients testing positive for Ki-67 (>2% nuclear staining) had a clinically malignant course while only 3 (7%) of the 41 cases with lower Ki-67 positivity rate behaved in a malignant fashion (P = .055). Ki-67-positive tumor had a significantly higher chance of harboring tumor necrosis than Ki-67-negative neoplasms (P < .01). There was no difference in staining between benign and malignant pheochromocytomas using p53, Bcl-2, mdm-2, cyclin D1, p21, and p27. (1) A PASS score of <4 predicted benign pheochromocytomas. (2) All malignant pheochromocytomas had a PASS score >/=6, which was significantly higher compared with the benign lesions. Patients with a PASS score >/=4 should be followed closely for recurrence. (3) p53, Bcl-2, mdm-2, cyclin D1, p21, and p27 appear to have no role in predicting the behavior of pheochromocytomas. Ki-67 may help identify those neoplasms at risk for recurrence by prompting the pathologist to look aggressively for adverse histologic features.

Predictive assay of neoadjuvant chemotherapy in management of oral cancer

Neoadjuvant chemotherapy (NAC) for oral squamous cell carcinoma has a positive impact on organ preservation and/or survival only in patients who achieve an excellent anti-tumour effect with this therapy. Predictive assay for NAC can play an important role in establishing tailor-made treatments for oral squamous cell carcinoma. In this retrospective study, the anti-tumour effects of cisplatin-based NAC in 70 patients with oral squamous cell carcinoma were reviewed in relation to biological markers of tumour cell proliferation activity: tumour grade, cellular DNA content, mitotic index, apoptotic index, ki-67 positive rate, and p53 and Bax expression. Tumour grade, Bax expression, apoptotic index and cellular DNA content were significantly correlated with the anti-tumour effects of NAC in univariate analysis. Tumour grade, Bax expression and apoptotic index were selected as independent predictive factors by means of multiple logistic analysis. Using the regression equation from these results, the prediction rate for anti-tumour effects was 70%. For patients in whom NAC is predicted to be ineffective, it may be necessary to choose another treatment option in order to improve their survival and quality of life.

Comparative effects of heparin-binding epidermal growth factor-like growth factor on the growth of cultured human uterine leiomyoma cells and myometrial cells

The objective of this study was to investigate the comparative effects of heparin-binding epidermal growth factor-like growth factor (HB-EGF) on the growth of cultured human leiomyoma cells and myometrial cells. Isolated cells were subcultured in Phenol Red-free Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum for 120 h and then stepped down to serum-free conditions for an additional 24 and 48 h in the presence or absence of graded concentrations of HB-EGF (0.1, 1, 10 and 100 ng/ml). These cells were used for immunocytochemical analysis for Ki67, western blot analysis for proliferating cell nuclear antigen (PCNA) and human EGF receptor (HER1), and TdT (terminal deoxynucleotidyl transferase)-mediated dUDP nick-end labelling (TUNEL) assay. Treatment with HB-EGF at concentrations >1 ng/ml significantly increased the Ki67-positive rate of cultured leiomyoma cells and myometrial cells. Treatment with HB-EGF also resulted in a dose-dependent increase in PCNA expression in both cells compared with untreated control cultures. A significant increase in PCNA expression in cultured myometrial cells was noted following treatment with HB-EGF at concentrations >1 ng/ml, whereas an increase in PCNA expression in cultured leiomyoma cells was noted following treatment with HB-EGF at concentrations >10 ng/ml. HER1 expression was significantly higher in untreated myometrial cells than in untreated leiomyoma cells. A significant increase in HER1 expression in myometrial cells was observed when treated with HB-EGF at concentrations >10 ng/ml, whereas a significant increase in HER1 expression in leiomyoma cells was noted only by the treatment with HB-EGF at concentrations >100 ng/ml. Treatment with HB-EGF decreased the TUNEL-positive rate of those cells with no significant differences between the two cell types. The results obtained suggest that HB-EGF plays a role in stimulating the proliferation of leiomyoma cells and myometrial cells and in inhibiting apoptosis of those cells through augmentation of HER1 expression. Since the proliferative potential of myometrial cells responded better to HB-EGF than that of leiomyoma cells, HB-EGF may play a more vital role in myometrial growth than leiomyoma growth.

Final Comments by the Authors

To investigate B7-H4 expression and its correlation with the number of infiltrating T lymphocytes and cytokine production by those lymphocytes in human cervical cancer and to determine the effect of recombinant B7-H4 on the active peripheral blood T cells of the patients in vitro.B7-H4 expression was detected in 67 cases of cervical cancer using immunohistochemical staining. Tumor-infiltrating CD8+T, CD4+T, and FOXP3+ (Forkhead Box P3) T lymphocytes and their levels of IFN-γ and TGF-β1 production were determined by immunofluorescent double-staining. After the peripheral blood T lymphocytes of patients were co-cultured with B7-H4, proliferation, apoptosis, and cell subtypes were analyzed using flow cytometry. Cytokines in the supernatant were detected by ELISA.B7-H4 was expressed in 46% (31/67) of the cases of cervical cancer. The number of infiltrating CD8+T lymphocytes and their IFN-γ production in positive B7-H4 expression cervical cancers was significantly lower than in negative B7-H4 cases (P < 0.01, P < 0.05), but there was no significant difference between cases positive and negative for B7-H4 with respect to infiltrating FOXP3+T and CD4+T cells or TGF-β1 production. After co-culture with B7-H4 for 48 h, the patients’ activated T lymphocytes were arrested at G1/G2 phase. The Ki67 positive rates of CD4+T and CD8+T cells were 2.13 ± 0.13% and 1.03 ± 1.33%, and they were lower than in the blank group. The proportion of CD4+T and CD8+T cells decreased, but CD4+T/CD8+T and the proportion of CD4+CD25+Foxp3+T cells increased. In addition, concentrations of IL-10 and TGF-β1 in the supernatant of co-cultured T cells increased significantly (P < 0.05, P < 0.05), but that of IFN-γ decreased. B7-H4 had no significant effect on apoptosis of the T cells.B7-H4 is overexpressed in human cervical cancers, and it is associated with lower numbers of tumor-infiltrating CD8+T lymphocytes and therefore less IFN-γ production. In vitro, B7-H4 inhibits the proliferation of CD4+T and CD8+T but promotes the proliferation of Tregs and the secretion of IL-10 and TGF-β1. B7-H4 plays an important role in depressing the anti-tumor immunity of CD8+T cell in microenvironments of cervical cancer.

A clinicopathologic study of 9 cases of primary pulmonary extranodal marginal zone B-cell lymphoma

To study the clinicopathologic and immunohistochemical features of primary pulmonary extranodal marginal zone B-cell lymphomas (MALT lymphomas). Immunohistochemical staining for LCA, CD20, CD45RO, CD5, cyclinD1, Ki-67, immunoglobine light chain κ and λ, CK and NSE was carried out in 9 patients with primary pulmonary extranodal marginal zone B-cell lymphomas by the S-P methods. According to the histological pattern and immunohistochemical features, all patients were diagnosed as primary pulmonary extranodal marginal zone B-cell lymphomas. There were four males and five females with a median age of 51.5 years (range from 37 to 64 years). The tumor cells were positive for LCA and CD20, however, the positive rates of Ki-67 were low. The tumor cells expressed immunoglobine light chain restriction λ in 5 cases , κ in 1 case, both λ and κ in 1 case, and neither of them in 2 cases. The tumor cells were negative for CD45RO, CD5, cyclineD1, CK, NSE in all patients. Primary pulmonary extranodal marginal zone B-cell lymphomas are inert lymphomas which are easily misdiagnosed. The evaluation of pathologic features and immunohistochemistry are useful and practical in the diagnosis and differential diagnosis of primary pulmonary extranodal marginal zone B-cell lymphomas.

Cell proliferation and cell death (apoptosis) in epithelial tumors of the stomach--analysis of tumor tissues by the endoscopic mucosal resection

To answer the question why some gastric cancers make elevation while others make depression in their early stage, and why polypoid cancers grow larger than their benign counterpart adenomas, the distribution of proliferating cells and apoptotic cells was compared between these lesions. Proliferating cells and apoptotic cells were detected with anti Ki-67 antibody (MIB-1) and with the in situ nick end labeling (ISNEL), respectively. A total of 62 gastric tumors, taken by the endoscopic mucosal resection method, was assessed. They consisted of 14 adenomas and 48 mucosal carcinomas (27 polypoid and 21 depressed type). Overall positive rates of Ki-67 were 27.5 +/- 9.0% in adenoma, 40.1 +/- 11.1% in polypoid cancer and 47.5 +/- 9.7% in depressed cancer. Proliferating cells were preferentially found in the cripts of metaplastic mucosa, in the middle to upper layer of adenomas, and in the whole layer including their surface of adenocarcinomas. Within cancers the polypoid type had more positive cells in the upper layer, so did the depressed type in the lower layer. ISNEL positive nuclei showed sphere, fragmented, ringed forms, or the same form as neighboring tumor nuclei. Apoptotic cells lay scattered throughout tumor glands. Apoptotic cell counts per 1000 tumor cells were 26.0 +/- 9.7 in adenoma, 36.3 +/- 32.1 in polypoid cancer, and 52.5 +/- 19.3 in depressed cancer. Depressed type cancers and a few polypoid cancers rich in non-tumor tissues showed higher numbers of apoptotic cells than adenomas and usual polypoid cancers. (ABSTRACT TRUNCATED AT 250 WORDS)

EXPRESSION OF HLA-DR ANTIGEN ON HEAD AND NECK CARCINOMAS

We investigated the expression of HLA-DR antigen on 42 squamous cell carcinomas of head and neck using immunohistological methods. Our results indicate significant relationships between HLA-DR antigen expression on carcinomas and lymphocytic infiltration, that is, CD8 positive lymphocytes (CD8/CD3) infiltrated HLA-DR antigen positive carcinomas while CD4 positive cells (CD4/CD3) were found in HLA-DR negative carcinoma. The Ki-67 (a nuclear marker of proliferation) positive rate was lower on HLA-DR positive carcinomas than on negative carcinomas. However, there was no correlation with pathological differentiation, clinical stage or primary lesion. In vitro studies using several cytokines showed that IFN-gamma induced expression of HLA-DR antigen and lowered the Ki-67 positive rate on squamous cell carcinomas. It seems that HLA-DR antigen expression on squamous cell carcinomas could be induced by cytokines released from the infiltrating lymphocytes.