Predominant expression of B7-H1 and its immunoregulatory roles in oral squamous cell carcinoma

We examined cell surface expression of five B7 costimulatory molecules (B7-H1, B7-DC, B7h, CD80 and CD86) in human oral squamous cell carcinoma (SCC) lines. Most human SCC cell lines expressed various levels of B7-H1 and B7-DC. Their expression was further upregulated by interferon (IFN)-gamma stimulation. Immunohistochemical staining revealed substantial and predominant expression of B7-H1 on human primary oral SCC. A murine SCC line, NR-S1, neither expressed B7-H1 nor B7-DC, but induced B7-H1 by IFN-gamma stimulation in culture and the inoculation in vivo. Although NR-S1 tumors grew progressively in immunocompetent syngeneic mice, the administration of blocking anti-B7-Hl or anti-PD-1 mAb significantly inhibited the tumor growth, suggesting the negative regulation of host immune responses by the PD-1:B7-H1 pathway. Our results demonstrate that B7-H1 is predominantly induced on oral SCC within the B7 family molecules. A successful inhibition of tumor growth by blockade of the PD-1:B7-H1 pathway may implicate a new approach for immunotherapy of oral SCC.     

B7-H1 expression on non-small cell lung cancer cells and its relationship with tumor-infiltrating lymphocytes and their PD-1 expression.

PURPOSE: B7-H1/PD-L1 (B7-H1) and B7-DC/PD-L2 (B7-DC) are ligands for the receptor PD-1, which is known to negatively regulate T-cell activation. In the present study, we investigated the expression of B7-H1 and B7-DC in tumor specimens of non-small cell lung cancer and their relationships with clinicopathological variables and postoperative survival. Furthermore, we examined the correlation between B7-H1 expression on tumor cells and the number of tumor-infiltrating lymphocytes (TILs) or PD-1 expression on TILs. EXPERIMENTAL DESIGN: The expression of B7-H1 and B7-DC in 52 surgically resected specimens of non-small cell lung cancer was evaluated immunohistochemically. RESULTS: Expression of B7-H1 and B7-DC was focally observed in all non-small cell lung cancer tumor specimens. No relationship was found between the expression of B7-H1 or B7-DC and clinicopathological variables or postoperative survival. However, in the same sections evaluated, significantly fewer TILs were identified in B7-H1-positive tumor regions than in B7-H1-negative tumor regions in a subset of five patients (P = 0.01). Moreover, the percentage of TILs expressing PD-1 was significantly lower in B7-H1-positive tumor regions than in B7-H1-negative tumor regions (P = 0.02). CONCLUSIONS: The expression of B7-H1 on tumor cells in local areas reciprocally correlated with the number of TILs, and this may contribute to negative regulation in antitumor immune responses in non-small cell lung cancer.     

Clinical significance and regulation of the costimulatory molecule B7-H1 in pancreatic cancer

We investigated the expression pattern and clinical significance of the costimulatory ligands B7-1, B7-2, B7-H1, and B7-DC, and their counter-receptors CTLA-4 and PD-1 in pancreatic cancer. Gene expression of all examined costimulatory molecules was significantly upregulated in pancreatic cancer tissues. B7-1, B7-2, B7-H1, and B7-DC protein was detectable in pancreatic cancer cells. Only the expression of B7-H1 significantly correlated with postoperative survival (p<0.0001). B7-H1 was inducible in cultured pancreatic cancer cells by IFN-gamma and significantly correlated with the level of IFN-gamma expression in human pancreatic cancer tissues (Spearman rho=0.4536,p=0.0029). B7-H1 positive tumors showed an increased prevalence of tumor-infiltrating regulatory T cells (T(regs)) compared to B7-H1 negative tumors. Among the investigated costimulatory molecules only tumor-associated B7-H1 seems to be of prognostic relevance in pancreatic cancer. B7-H1 might, therefore, be involved in the downregulation of antitumor responses through regulation of T(regs) in pancreatic cancer. Our findings also suggest a dual role of IFN-gamma in antitumor response. Through induction of B7-H1 in pancreatic cancer cells IFN-gamma might contribute to the evasion of antitumor immunity.     

B7-h4 is highly expressed in ductal and lobular breast cancer.

PURPOSE: This study was designed to investigate the expression of B7-H4 protein, a member of the B7 family that is involved in the regulation of antigen-specific immune responses, in normal breast and in primary and metastatic breast carcinomas. EXPERIMENTAL DESIGN: Archival formalin-fixed tissue blocks from breast cancers and normal somatic tissues were evaluated for B7-H4 expression by immunohistochemistry with manual and automated image analysis. The proportion of B7-H4-positive cells and the intensity of B7-H4 staining were compared with histologic type, grade, stage, hormone receptor status, and HER-2/neu status. RESULTS: B7-H4 was detected in 165 of 173 (95.4%) primary breast cancers and in 240 of 246 (97.6%) metastatic breast cancers. B7-H4 staining intensity was greater in invasive ductal carcinomas [24.61 relative units (RU)] and in invasive lobular carcinomas (15.23 RU) than in normal breast epithelium (4.30 RU, P = 0.0003). Increased staining intensity was associated with negative progesterone receptor status (P = 0.014) and history of neoadjuvant chemotherapy (P = 0.004), and the proportion of B7-H4-positive cells was associated with negative progesterone receptor (P = 0.001) and negative HER-2/neu (P = 0.024) status. However, there was no statistically significant relationship between the proportion of B7-H4-positive cells or staining intensity and grade, stage, or other clinicopathologic variables. Low levels of B7-H4 expression were also detected in epithelial cells of the female genital tract, lung, pancreas, and kidney, but B7-H4 was generally absent in most other normal somatic tissues. CONCLUSIONS: The nearly ubiquitous expression of B7-H4 in breast cancer, independent of tumor grade or stage, suggests a critical role for this protein in breast cancer biology.     

A novel monoclonal antibody (7B10) with differential reactivity between human mammary carcinoma and normal breast

A monoclonal antibody (7B10) which displays differential reactivity with breast carcinomas compared to benign lesions or normal breast tissue was selected by fusion of spleen cells from BALB/c mice immunized with the T47D human mammary carcinoma cell line. The antigen, recognized by 7B10 on T47D cells, appeared to be both surface and cytoplasm localized, as demonstrated by indirect immunofluorescence, immunoperoxidase, and electron microscopy studies. This antibody (IgG1) bound with four human breast cancer cell lines (T47D, MCF7, ZR-75-1, and HSL53) which express estrogen receptors. No binding was observed with cancer cell lines of other origin or with normal cells. In vivo, by immunoperoxidase staining of frozen sections of normal breast, the antigen recognized by 7B10 appeared to be located on epithelial cell membranes, whereas in benign and malignant mammary disorders, staining also involved the cytoplasm, as confirmed by electron microscopy on fresh cancer tissue. On formalin-fixed, paraffin-embedded sections, cytoplasmic staining was detected in breast cancer, but no immunostaining was observed with benign lesions or normal breast. In paraffin sections, most normal tissues investigated did not react with 7B10 antibody. However, ducts in the parotid gland, tubules in the kidney and some biliary ducts, and apocrine glands in the skin showed irregular, diffuse weak staining. 7B10 was unreactive with adenocarcinomas of origin other than breast, except for some cells in ovarian clear cell carcinoma. No reactivity was observed with squamous carcinomas, lymphomas, or melanomas. The antigen recognized by 7B10 appeared to be a Mr 32,000 protein, as identified by immunoprecipitation from extracts of T47D after labeling with [35S]methionine. Since the antigen was present only on the membrane of differentiated normal mammary epithelial cells, and was also expressed in the cytoplasm of tumor cells, it may be of interest in immunological studies of mammary epithelial cell differentiation. Moreover, since in formalin-fixed tissues immunostaining is virtually confined to mammary carcinomas, monoclonal antibody 7B10 may have diagnostic applications in breast cancer.     

12-O-tetradecanoyl phorbol 13-acetate induces the expression of B7-DC, -H1, -H2, and -H3 in K562 cells

Induction of the B7 family molecules by 12-O-tetradecanoyl phorbol 13-acetate (TPA) has been reported, however, the mechanism by which TPA up-regulates these molecules remains poorly understood. In this study, the expression of B7-DC, -H1, -H2, and -H3 in response to TPA was markedly induced in K562 cells. TPA also induced activation of ERK, p38 mitogen-activated protein kinase (MAPK), JNK, phosphatidylinositol-3-kinase (PI-3K), or nuclear factor (NF)-kappaB. Pre-treatments with protein kinase C (PKC) inhibitors significantly inhibited TPA-induced expression of B7-DC, -H1, -H2, and -H3 mRNA as well as TPA-induced phosphorylation of ERK, p38 MAPK, JNK, and PI-3K. TPA-induced expression of B7-DC, -H1, -H2, and -H3 mRNA was abrogated by pre-treatments with inhibitors of ERK and p38 MAPK. However, inhibition of PI-3K and JNK only caused decrease of TPA-induced B7-DC mRNA and B7-H3 mRNA, respectively. TPA-induced degradation of IkappaB-alpha was markedly abrogated by treatments with PKC inhibitors, but not by treatments with inhibitors of ERK, p38 MAPK, JNK, or PI-3K. NF-kappaB inhibitors significantly attenuated the expression of B7-DC, -H1, -H2, and -H3 mRNA in response to TPA. These results suggest that TPA induces the expression of B7-DC, -H1, -H2, and -H3 mRNA in K562 cells via activation of PKC, ERK, p38 MAPK, and NF-kappaB. Distinctly, the expression of B7-DC mRNA and -H3 mRNA in response to TPA is also PI-3K- and JNK-dependent, respectively.     

负性共刺激分子B7-H1和B7-H4在结直肠癌中的表达及其临床意义

目的:检测结直肠癌组织中负性共刺激分子B7-H1和B7-H4的表达、T细胞亚群的浸润情况,探讨其临床意义。方法:收集苏州大学附属第四医院2003年1月至2003年12月50例结直肠癌患者的癌组织标本以及5例患者的癌旁组织标本,免疫组织化学法检测结直肠癌组织中B7-H1和B7-H4的表达以及T细胞亚群的浸润,分析B7-H1、B7-H4的表达与结直肠癌患者临床病理特征及T细胞浸润的相关性,分析B7-H1、B7-H4的表达和CD3+T、CD8+T淋巴细胞浸润程度与患者预后的相关性。结果:结直肠癌组织高表达B7-H1(44%)和B7-H4(56%),而癌旁组织不表达(P<0.01)。B7-H1在结肠癌组织中的表达较直肠癌显著升高(P<0.05);随着Duke’s分期的升高,B7-H4的表达水平也呈上升趋势(P<0.05)。结直肠癌组织中B7-H1的表达与CD3+T细胞浸润呈负相关(P<0.05),但与B7-H4的表达无关。B7-H1的表达水平与患者预后呈负相关(P<0.05),且B7-H1和B7-H4同时高表达的患者总体生存率显著降低(P<0.05)。结论:负性共刺激分子B7-H1和B7-H4在人结直肠癌组织中高表达,并与患者总体生存率相关,两者的共同检测对结直肠癌诊断和预后判断具有一定的临床价值。     

皮肤恶性肿瘤组织中B7-H1的表达及临床意义

目的 研究共刺激分子B7-H1在常见皮肤恶性肿瘤组织中的表达及其临床意义。方法 采用ElivsionTMplus免疫组织化学法检测B7-H1在51例鳞状细胞癌（SCC组）和93例非鳞状细胞癌共144例皮肤恶性肿瘤组织中的表达情况,同时选取10例日光性角化病（癌前病变组）和10例皮肤良性肿瘤（良性肿瘤组）作对照,分析B7-H1在癌前病变组、良性肿瘤组、SCC组及非鳞状细胞癌中的阳性表达率以及SCC中B7-H1表达水平与临床病理参数（年龄、性别、肿瘤大小、肿瘤部位、曝光部位及分化程度）间的关系。结果 B7-H1主要表达于皮肤肿瘤细胞的胞质及胞膜,呈弥漫性棕黄色颗粒状染色。B7-H1在癌前病变组、良性肿瘤组及SCC组的阳性表达率分别为10.0％（1／10）、40.0％（4／10）和76.5％（39／51）;在SCC中,B7-H1表达水平在不同年龄、性别、肿瘤大小、肿瘤部位、曝光部位及分化程度间的差异均无统计学意义（P＞0.05）。B7-H1在常见上皮来源的非鳞状细胞癌中均有表达,其中基底细胞癌、汗腺癌、乳房外Paget病、腺样囊性癌、皮脂腺癌及恶性黑色素瘤的阳性表达率依次为81.4％（35／43）、70.0％（7／10）、100.0％（3／3）、100.0％（2／2）、100.0％（1／1）和76.2％（16／21）。而在非上皮来源的隆突性纤维肉瘤中未见表达。结论 皮肤SCC组织中B7-H1表达率高于癌前病变和皮肤良性肿瘤组织,提示B7-H1可能参与了皮肤恶性肿瘤的发生与发展。     

协同刺激分子B7-H4在小鼠食管癌前病变中的表达

目的：研究协同刺激分子B7同系物4（B7-H4）在小鼠食管癌前病变中的表达变化,探讨其在食管鳞状细胞癌发生中的作用。方法：133只C57BL/6小鼠,分为对照组42只和诱癌组91只。诱癌组小鼠采用饮水法给予50 μg/mL 4-硝基喹啉-1-氧化物（4NQO）15周,诱导小鼠食管癌前病变。通过苏木素-伊红（HE）染色法评价食管组织病理变化;免疫组化和Western blot检测B7-H4蛋白在食管组织中的表达,Western blot检测B7-H4蛋白在小鼠血清中的表达。结果：从16~28周,4NQO诱癌组小鼠食管组织出现肉眼可见的增厚、凸起、肿块等病理改变。HE染色结果显示,小鼠食管组织癌前病变级别与诱癌时间呈正相关（r=0.55,P < 0.01）。另外,B7-H4在食管组织的表达水平与食管癌前病变级别呈正相关（r=0.57,P < 0.01）。与对照组相比,第26周和第28周诱癌组小鼠食管组织B7-H4蛋白表达显著升高（P < 0.05或P < 0.01）。与正常小鼠相比,高级别上皮内瘤变小鼠血清B7-H4蛋白浓度显著升高（P < 0.05）。结论：小鼠食管癌前病变进程中,B7-H4蛋白在血清和食管组织中表达上调,B7-H4可能参与了食管癌前病变的进程。     

协同刺激分子B7-H4在食管癌前病变组织中的表达及临床意义

目的：研究协同刺激分子B7同系物4（B7-H4）在人食管癌前病变组织中的表达变化,探讨其在食管鳞状细胞癌形成中的临床意义。方法：收集内镜切除的食管组织标本58例,其中正常组织16例,低级别上皮内瘤变（LGIN）23例,高级别上皮内瘤变（HGIN）19例。通过苏木素-伊红（HE）染色评价食管组织病理变化。分别采用实时荧光定量PCR（qPCR）检测B7-H4 mRNA在食管组织的表达;免疫组织化学和Western blot检测B7-H4蛋白在食管病变组织中的表达;酶联免疫吸附法（ELISA）检测食管组织细胞因子IL-6、IL-10和IFN-γ的表达,并分析各细胞因子与B7-H4蛋白表达的相关性。结果：免疫组化和HE染色结果提示,B7-H4表达与食管组织病理分级呈显著正相关（P < 0.01）。qPCR结果提示,与正常食管组织相比,食管癌前病变组织B7-H4 mRNA表达无显著改变（P > 0.05）。而Western blot实验结果显示,与正常食管组织相比,食管癌前病变组织B7-H4蛋白表达显著升高（P < 0.05）。Westernblot和ELISA实验结果显示B7-H4表达与IL-6表达呈正相关（P < 0.01）。结论：随着食管癌前病变病理分级的提高,B7-H4蛋白的表达逐渐上调,B7-H4可能与IL-6相互作用促进了食管鳞状细胞癌的发生发展。     

Tumor B7-H1 and B7-H3 Expression in Squamous Cell Carcinoma of the Lung

BackgroundPulmonary squamous cell carcinoma has a poor prognosis, and new therapeutic targets are needed. The aberrant expression of the immunomodulatory proteins B7-H1 and B7-H3 by malignant cells may contribute to tumoral immune evasion. Data about the expression of these proteins by squamous cell carcinoma of the lung are limited.Materials and MethodsImmunohistochemistry for B7-H1 and B7-H3 was performed on 214 resected pulmonary squamous cell carcinoma specimens.ResultsAt the last follow-up, 171 of 214 (80%) of patients were deceased (median survival time, 3.76 years). Forty-two (19.6%) of 214 cases showed positivity with B7-H1, with a range of 5% to 60% of cells that stained positively. A total of 189 (88.3%) of 214 cases showed positivity with B7-H3, with a range of 5% to 80% of cells staining positively. By using multivariate analysis, no degree of B7-H1 or B7-H3 positivity was significantly associated with patient outcome.ConclusionsAlthough B7-H1 and B7-H3 are not of independent prognostic value, they are commonly expressed on a subset of tumor cells in pulmonary squamous cell carcinomas. Known interaction of the B7-H proteins with cytotoxic T-lymphocyte antigen-4 may make them attractive candidate biomarkers for response to immunomodulatory therapeutics, eg, ipilimumab, and warrants further study.     

B7-H3 ligand expression by prostate cancer: a novel marker of prognosis and potential target for therapy

B7 coregulatory ligands can be aberrantly expressed in human disease. In the context of cancer, these ligands may act as antigen-specific inhibitors of T-cell-mediated antitumoral immunity. We recently reported that B7-H1 expression by carcinomas of the kidney and bladder portends aggressive disease and diminished survival. The expression of these proteins in prostate cancer, however, has not been investigated. We evaluated B7-H3 and B7-H1 protein expression in the pathologic specimens of 338 men treated for clinically localized prostate cancer between 1995 and 1998 with radical retropubic prostatectomy. Expression levels of B7-H3 in prostate cancer were correlated with pathologic indicators of aggressive cancer as well as clinical outcome. We report that B7-H3 is uniformly and aberrantly expressed by adenocarcinomas of the prostate, high-grade prostatic intraepithelial neoplasia, and four prostate cancer cell lines, whereas B7-H1 is rarely expressed. B7-H3 is expressed by benign prostatic epithelia, although at a more reduced level relative to neoplastic tissue. Increasing levels of B7-H3 intensity correlate with worsening clinicopathologic features of prostate cancer. Marked B7-H3 intensity, present in 67 (19.8%) specimens, confers a >4-fold increased risk of cancer progression after surgery (risk ratio, 4.42; P < 0.001). A survey of normal tissues revealed that B7-H3 is expressed within the liver, urothelium, and fetal kidney. In summary, B7-H3 is aberrantly expressed in all prostate cancers and represents an independent predictor of cancer progression following surgery. Moreover, B7-H3 encompasses a novel diagnostic and potential therapeutic target for the clinical management of prostate cancer and, perhaps, other malignancies as well.     

Expression of B7-H3 in hypopharyngeal squamous cell carcinoma as a predictive indicator for tumor metastasis and prognosis

B7-H3 is a member of the B7 family thought to be a co-regulatory factor of antigen-specific T-cell immune response via co-stimulatory and co-inhibitory receptors. We evaluated its potential expression in head and squamous cell carcinoma (SCC) cell lines, and in clinical tissue samples obtained from 37 patients with human hypopharyngeal SCC. All head and neck SCC cell lines tested expressed both the B7-H3 gene and cell surface protein. The staining intensity of immunoreactivity by tumor cells was blindly evaluated by two head and neck surgeons and the results were categorized into 4 grades according to staining intensity. Eighty-seven percent of patients expressed B7-H3. B7-H3 expression was inversely correlated with the number of tumor infiltrating CD8+ T-cells (r=-0.4339, p=0.023). Patients who developed distant metastasis after tumor-free periods showed significantly higher B7-H3 expression scores compared to patients who did not develop distant metastasis during follow-up periods (p=0.048). Distant metastasis control ratio in patients with strong B7-H3 expression was significantly lower compared to that in patients with no to intermediate B7-H3 expression (p=0.040). Cause-specific survival ratio in patients with strong B7-H3 expression was significantly lower compared to that in patients with no to intermediate B7-H3 expression (p=0.028). Moreover, multivariate analysis revealed that strong B7-H3 expression was an independent prognostic factor in tumor-specific death in hypopharyngeal SCC (hazard ratio: 9.803, confidence interval: 0.018-0.539, p=0.0110).     

Significance of heterogeneous nuclear ribonucleoprotein B1 as a new early detection marker for oral squamous cell carcinoma.

The development of an early tumor detection marker for oral cancer is an obvious need due to the high recurrence rate and poor survival rate. Based on our previous report that overexpression of heterogeneous nuclear ribonucleoprotein (hnRNP) B1 protein was found in 100% of squamous cell carcinomas of human lung, we applied the same immunohistochemical method, using anti-hnRNP B1 antibody, to human oral squamous cell carcinoma (OSCC). Seven human tissue sections of OSCC showed strong staining with anti-hnRNP B1 antibody, and hnRNP B1 protein of 37 kDa was identified in protein fractions isolated from six of the cancerous tissue sections, while it was not found in adjacent noncancerous tissue. Moreover, three non-homogeneous (nodular) leukoplakia sections showed significant anti-hnRNP B1 staining. The results suggest that this antibody detects precancerous lesions as well as advanced lesions (stages I to IV) of OSCC. We also present positive results of cytodiagnosis for two smear specimens. All of the above results indicate that hnRNP B1 is a new and useful marker for early detection of OSCC.     

Significance of Heterogeneous Nuclear Ribonucleoprotein B1 as a New Early Detection Marker for Oral Squamous Cell Carcinoma

The development of an early tumor detection marker for oral cancer is an obvious need due to the high recurrence rate and poor survival rate. Based on our previous report that overexpression of heterogeneous nuclear ribonucleoprotein (hnRNP) B1 protein was found in 100% of squamous cell carcinomas of human lung, we applied the same immunohistochemical method, using anti-hnRNP B1 antibody, to human oral squamous cell carcinoma (OSCC). Seven human tissue sections of OSCC showed strong staining with anti-hnRNP B1 antibody, and hnRNP B1 protein of 37 kDa was identified in protein fractions isolated from six of the cancerous tissue sections, while it was not found in adjacent noncancerous tissue. Moreover, three non-homogeneous (nodular) leukoplakia sections showed significant anti-hnRNP B1 staining. The results suggest that this antibody detects precancerous lesions as well as advanced lesions (stages I to IV) of OSCC. We also present positive results of cytodiagnosis for two smear specimens. All of the above results indicate that hnRNP B1 is a new and useful marker for early detection of OSCC.     

Coexpression of cytokeratins 7 and 20 confirms urothelial carcinoma presenting as an intrarenal tumor

BACKGROUND: The differentiation of epithelial tumors arising in the kidney (urothelial vs. renal cell carcinoma) sometimes can be difficult by clinical and radiologic studies. Because urothelial and renal epithelium express unique cytokeratin (CK) 7 and 20 profiles, the authors studied the utility of these markers to confirm the diagnosis of urothelial carcinomas that present clinically as kidney masses. METHODS: Using commercially available monoclonal antibodies, paraffin section immunohistochemistry was used to examine two recent cases of urothelial carcinomas presenting as renal tumors. Tissues were stained for CK7 and CK20 and the expression compared between the tumor and benign tissue. RESULTS: Both cases showed solid renal masses that clinically and radiographically could have been of renal cell origin, but subsequently were confirmed histologically to be extensive renal involvement by urothelial carcinoma. The tumors coexpressed both CK7 and CK20, which is the expected profile for carcinomas of urothelial but not renal origin. CONCLUSIONS: The results of the current study show that coexpression of CK7 and CK20 is a useful diagnostic aid in the differential diagnosis of epithelial kidney tumors of urothelial cell versus renal cell origin.     

B7-H4在上皮性卵巢癌中的表达及意义

目的 探讨上皮性卵巢癌组织中B7-H4的表达及其与临床病理特征和预后的关系。方法采用免疫组化法检测66例上皮性卵巢癌、5例交界性卵巢肿瘤、8例良性卵巢肿瘤组织和20例正常卵巢组织蜡块中B7-H4的表达,分析其表达与上皮性卵巢癌临床病理特征和预后的关系。结果 B7-H4在上皮性卵巢癌组织中的阳性表达率为86.4％,在卵巢交界性肿瘤、卵巢良性肿瘤及正常卵巢组织中均不表达。B7-H4在浆液性囊腺癌、子宫内膜样癌和透明细胞癌中的阳性表达率分别为100.0％、90.0％和87.5％,均高于其在黏液性囊腺癌中的50.0％,差异有统计学意义（P＜0.05）。上皮性卵巢癌中B7-H4的表达与年龄、腹水细胞学无关,而与临床FIGO分期、组织学分级、淋巴结转移有关。B7-H4的表达与上皮性卵巢癌患者的生存情况无关（P＞0.05）。结论 B7-H4蛋白在上皮性卵巢癌组织中的表达上调,其表达与上皮性卵巢癌的发生、发展有关。     

B7-H4在卵巢浆液性癌组织中的表达及其临床意义

目的探讨B7-H4在卵巢上皮性肿瘤浆液性癌中的表达情况及其临床意义。方法应用逆转录聚合酶链反应(RT-PCR)技术及采用免疫组织化学PV-9000二步法,检测40例卵巢浆液性癌、20例交界性卵巢浆液性肿瘤和15例卵巢浆液性囊腺瘤组织中B7-H4mRNA及B7-H4蛋白表达情况。结果 B7-H4mRNA在卵巢浆液性癌、交界性卵巢浆液性肿瘤和卵巢浆液性囊腺瘤组织中均有表达;B7-H4蛋白表达于卵巢浆液性肿瘤细胞胞质和(或)胞膜,卵巢浆液性癌、交界性卵巢浆液性肿瘤和卵巢浆液性囊腺瘤组织中其阳性表达率分别为75.0%(30/40)、50.0%(10/20)和13.3%(2/15),阳性率逐级下降,差异均有统计学意义(P<0.05)。B7-H4蛋白表达与卵巢浆液性癌临床分期、病理分级、患者年龄、腹腔积液细胞学和淋巴结转移无相关性(P>0.05)。结论 B7-H4在卵巢浆液性癌组织中高表达,提示其可能与肿瘤的发生发展有关,可为卵巢恶性肿瘤的诊断及治疗提供新策略。     

协同刺激分子PD-L1、B7-H3与B7-H4在卵巢癌中的表达及其意义

协同刺激分子PD-L1、B7-H3与B7-H4可与T细胞及其受体结合并抑制T细胞的增殖和过度活化,在细胞免疫应答过程中起重要的调控作用,已被多项研究证明与肿瘤的免疫原性及肿瘤的发生、发展密切相关。这3种分子在正常卵巢组织中均不表达,而在卵巢癌组织中呈不同程度的高表达,它们可能在促进卵巢癌的发生、转变及病情进展过程中起重要作用,研究其作用机制对卵巢癌的早期诊断及靶向治疗有一定的意义。