Expression of type 1 and type 2 blood group-related antigens in normal and neoplastic gastric mucosa

The distribution of the blood group-related antigens type 1 (Lewis(a) [Le(a)], Lewis(b) [Le(b)]) and type 2 (H type 2, Y) has been examined in histologically normal and malignant mucosa of 40 surgical specimens of patients with adenocarcinoma of the stomach, with the use of a panel of monoclonal antibodies. Patients' Lewis phenotype and secretor status are correlated to the authors' findings. The surface epithelium of normal pyloric and fundic mucosa expressed the Lewis isoantigen (Le(a) in Le[a+b-] phenotype and Le(b) in Le[a-b+] phenotype), whereas the deep areas of this mucosa no showed the Le(a), Le(b) antigens and expressed the Y and H type 2 antigens whatever the secretor status of patients. Nineteen of 24 patients with Le(a-b+) phenotype showed anomalous expression of Lea antigen in neoplastic cells. In three of them, this alteration was found in tumor adjacent mucosa. No expression of Le(a) or Le(b) antigens was found in tumors or normal mucosa from Le(a-b-) phenotype patients.     

Comparative study on the expression of the blood group antigens Le a,Le b,Le x,Le y and the carbohydrate antigens CA 19-9 and CA-50 in chronic pancreatitis and pancreatic carcinoma

Summary The expression of the blood group antigens Le a, Le b, Le x, Le y and the carbohydrate antigens CA 19-9 and CA-50 was studied in 20 ductal pancreatic carcinomas, 24 pancreases with chronic pancreatitis and 10 normal fetal and adult pancreases. CA 19-9, CA-50 and Le a showed the strongest staining intensity, the highest percentage of labelled cells, and a membrane-bound expression pattern in epithelial cells of normal pancreas, chronic pancreatitis and well differentiated (G1) carcinoma; in moderately and poorly differentiated carcinomas (G2/3) it was predominantly cytoplasmic. The staining pattern of Le b and Le x was less clearly membrane-bound but varied with cytoplasmic and Golgi-located distributions in all pancreatic specimens. Le y revealed a consistent granular antigen expression in the Golgi-region of ductal epithelial, acinar and carcinoma cells.None of the antibodies allowed a morphological differentiation by their expression pattern between hyperplastic, metaplastic and dysplastic or neoplastic cells. The differences in their staining patterns were quantitative and did not allow a qualitative differentiation between chronic pancreatitis and pancreatic carcinoma.We found coexpression of Le a and Le b antigens in 46/54 pancreatic specimens. All but 7 pancreata were CA 19-9 positive. An association between Le x, y and Le a, b antigen expression could not be noted in our material.supported by the Johannes and Frieda Marohn Foundation Erlangen     

Immunohistochemical study of colorectal adenomas with monoclonal antibodies against blood group antigens (sialosyl-Le(a), Le(a), Le(b), Le(x), Le(y), A, B, and H)

We studied 40 colorectal adenomas with monoclonal antibodies against blood group antigens (sialosyl-Le(a), Le(a), Le(b), Le(x), Le(y), A, B, and H). Sialosyl-Le(a), Le(a), Le(x), and Le(y) are usually present in different compartments of the crypts of normal colorectum and can be considered markers of normal differentiation antigens (NDA). The former two antigens represent markers for differentiated colonic epithelium and the latter two, markers for "undifferentiated" crypt base epithelium. Le(b), A, B, and H are normally absent from the distal colon and rectum, but are expressed by fetal colon and carcinomas and are considered oncofetal tumor-associated antigens (OF-TAA). Individual adenomas could be characterized as to whether or not they expressed OF-TAA and NDA. Of the adenomas, 35% were OF-TAA+/NDA+, 40% were OF-TAA+/NDA-, 17.5% were OF-TAA-/NDA+, and 7.5% were OF-TAA-/NDA-. When NDA were present, they were expressed in the same compartment of the crypt as in the normal colon and rectum. In adenomas there was proliferation of the undifferentiated enterocyte marker Lex throughout the entire length of the crypt when compared with controls (p less than 0.01). Of the adenomas, 75% expressed OF-TAA, however, 35% of adenomas concomitantly expressed NDA in the same distribution as normal colon and rectum indicating that adenomas have features of both carcinoma and normal colorectum epithelium.     

The expression of CEA, CA 19-9 and HMFG antigens in ovarian clear-cell and endometrioid carcinomas.

The tumour antigen expression of ovarian and endometrial endometrioid carcinomas, ovarian clear-cell carcinomas as well as endometrial and cervical clear-cell carcinomas were immunohistochemically compared. Of special interest were potential differences between the endometrioid and clear-cell carcinomas of the ovary. The expression of CEA and CA 19-9 tumour antigens in all these tumour types was heterogeneous, with 10-20% of the cases being positive for CEA and 40-75% being positive for CA 19-9. In contrast, HMFG IIIC 12, a monoclonal antibody originally directed against human milk fat globule (HMFG) membrane antigens, invariably detected a corresponding antigen on every case of these tumour types. Another HMFG antibody, SM IF 3, on the other hand, detected antigenic material on all clear-cell tumour types, but only rarely on endometrioid tumours of the ovary or endometrium. While HMFG IIIC 12 detects an antigen present on all ovarian, endometrial and mammary carcinomas, antibody SM IF 3 thus appears to be more restricted in its staining patterns. Our results with both of these antibodies indicate that ovarian clear-cell carcinomas and ovarian endometrioid carcinomas have antigenic differences, which provides further evidence that they belong to different tumour entities.     

血清CA19-9、sICAM-1、LDH在结直肠癌患者血清中的表达及其用于预后评估的价值

目的探讨血清CA19-9、sICAM-1、LDH在结直肠癌患者血清中的表达及其用于预后评估的价值。方法选取我院于2013年1月至2015年1月诊断的120例结直肠癌患者作为研究对象,另选我院同期体检正常者110例为对照组研究对象。对所有研究对象进行入院后血清CA19-9、sICAM-1、LDH水平检测,随后在患者入院后展开为期5年的随访,分析两组血清CA19-9、sICAM-1、LDH水平差异,研究组患者血清CA19-9、sICAM-1、LDH水平与患者病理特征差异,研究组患者血清CA19-9、sICAM-1、LDH水平与临床分期、临床分型、随访情况的相关性以及Logistic分析。结果研究组患者血清CA19-9、sICAM-1、LDH水平明显高于健康对照组(P <0.05);研究组患者临床分期Ⅲ期和临床随访死亡患者的CA19-9、sICAM-1、LDH水平明显高于Ⅱ期患者和临床随访生存患者(P<0.05)。不同临床分型研究组患者血清CA19-9、sICAM-1、LDH水平从高到低依次为侵润型、溃疡型、肿块型(P<0.05);患者血清CA19-9、sICAM-1、LDH水平越高,患者临床分期、临床分型以及随访死亡情况越为严重(P <0.05);血清CA19-9、sICAM-1、LDH均为结直肠癌患者五年生存的独立危险因素。结论血清CA19-9、sICAM-1、LDH与结直肠癌患者临床分期、临床分型以及生存情况密切相关,对于患者的预后预测具有积极意义。     

血清CA19-9、CEA水平与胰腺癌预后的关系

目的:探讨胰腺癌患术前血清中CA19-9与CEA表达情况对预后的影响.方法:回顾分析医院2012年1月~2013年12月128例胰腺癌患临床病理资料,应用Kaplan-Meier法、Log-rank检验及Cox回归分析CA19-9和CEA水平与患生存时间的关系.血清中CA19-9 >39 U/mL,CEA >4.7 ng/mL被视为表达增高.结果:128例患平均年龄为62岁,中位生存期为12.2月,其中CA19-9和CEA的表达水平增高的比例分别为78.1%,37.5%.CA19-9、CEA升高组患的预后明显差于正常组(CA19-9, P=0.027;CEA,P=0.036).Cox多因素回归分析显示淋巴结转移、CA19-9 >39 U/mL、CEA >4.7 ng/mL是影响胰腺癌患预后的独立因素.结论:术前CA19-9、CEA水平与胰腺患生存时间密切相关,能有效评估患的预后.     

血清CA19-9、CA125、CEA、CYFRA21-1、CA15-3和Galectin-3在胰腺病变鉴别诊断中的作用

目的探讨血清CA19-9、CA125、CEA、CYFRA21-1、CA15-3和Galectin-3的单项检测和联合检测在胰腺病变鉴别诊断中的作用。方法用雅培ARCHITECT i2000化学发光免疫分析仪分别检测125例胰腺导管腺癌患者和115例胰腺炎患者血清中的CA19-9、CA125、CEA、CYFRA21-1、CA15-3和Galectin-3水平。结果经受试者工作特征曲线(receiver operating characteristic curve,ROC)分析,CA19-9的曲线下面积(area under the curve,AUC)最大,为0.856,灵敏度和特异性分别75.2%和92.2%,其次为CA125(AUC=0.706),CEA(AUC=0.689)和CYFRA21-1(AUC=0.672)。而CA15-3(AUC=0.568)和Galectin-3(AUC=0.537)很难鉴别胰腺癌和胰腺炎。CA19-9、CA125和CEA联合检测的AUC为0.910,灵敏度和特异性分别为77.6%和93.9%,均高于CA19-9单项指标。CA125和CYFRA21-1在胰腺癌晚期组的血清水平明显高于早期组(P<0.05),而其他四项指标没有显著差异(P>0.05)。结论血清CA19-9在胰腺病变鉴别诊断中具有重要的价值,而Galectin-3的价值不高,血清CA19-9、CA125和CEA的联合检测可提高CA19-9单项对胰腺癌的诊断效能。CA125和CYFRA21-1和胰腺癌的肿瘤分期相关。     

Immunohistological patterns of blood group ABO and type 1 chain (Lewis a Lewis b) and type 2 chain (H-2, Y) antigens in normal uterine cervix

Ten monoclonal antibodies and one lectin were used to study the localization and distribution of Blood Group ABH, type 1 chain (Lewis a, Lewis b) and type 2 chain (H-2, Y) antigens in 22 cases of normal uterine cervix, with known ABO and Lewis phenotype and secretor status. The results showed that ABH isoantigen expression is clearly related to the secretor status. It is positive in the endo- and exocervical epithelium of secretor individuals and negative in non-secretors. Lewis antigen expression in both endocervical and exocervical epithelium is related to the patient's Lewis phenotype and is clearly controlled by the secretor gene. Indeed, the expression of the Lewis a antigen is limited to the tissue of people of Lewis (a + b-) phenotype (non-secretors), and the expression of Lewis b antigen is limited to the tissue of people of Lewis a-b+) phenotype (secretors). The Y antigen showed a focal expression in endocervical mucosa in all the cases, independently of secretor status or Lewis phenotype. The same pattern was observed for H-type 2 antigen, though only in secretor individuals.     

Immunocytochemical evaluation of HBME-1, CA 19-9, and CD-15 (Leu-M1) in fine-needle aspirates of thyroid nodules

Overlapping morphologic patterns that may be observed in goiter, follicular adenoma, and papillary carcinoma can limit the cytologic evaluation of the thyroid gland. In an attempt to develop a useful adjunctive test, the immunocytochemical reactivity of HBME-1, carcinoma antigen 19-9 (CA 19-9), and CD-15 (Leu-M1) was tested on 59 cell block preparations from fine-needle aspirations of the thyroid gland. HBME-1 monoclonal antibody was reactive in all 21 papillary carcinomas, in 4 of 18 adenomas, and in 5 of 20 goiters. CA 19-9 was identified in 13 of 21 carcinomas, 1 goiter, but none of the adenomas. CD-15 was present in 15 of 21 carcinomas, 1 goiter, and 1 adenoma. We conclude that HBME-1 is a sensitive marker of papillary thyroid carcinoma. CD-15 and CA 19-9 are less sensitive but more specific. This panel can be useful to help classify morphologically equivocal lesions. As with all immunocytochemical testing, caution must be exercised in the interpretation of results, and correlation made with morphologic and clinical data. Diagn. Cytopathol. 1998;18:93–97. © 1998 Wiley-Liss, Inc.     

Combined detection of preoperative serum CEA,CA19-9 and CA242 improve prognostic prediction of surgically treated colorectal cancer patients

We assessed the prognostic significance of preoperative serum carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9) and carbohydrate antigen 242 (CA242) levels in surgically treated colorectal cancer patients. The relationship of preoperative serum CEA, CA19-9 and CA242 levels with disease characteristics was investigated in 310 patients. Correlation between tumor markers was investigated using Pearson correlation test. Univariate and multivariate survival analyses were used to study the relationship between preoperative tumor markers and prognosis [disease free survival (DFS) and overall survival (OS)]. Kaplan-Meier analysis with log rank test was used to assess the impact of tumor marker levels on survival. Positive rate of preoperative serum CEA, CA19-9 and CA242 were 54.84%, 47.42% and 37.10%, respectively. High preoperative CEA level was associated with tumor size (P = 0.038), T stage (P < 0.001) and AJCC stage (P = 0.002). High preoperative CA19-9 level was associated with tumor AJCC stage (P = 0.023). Preoperative CA242 positively correlated with CEA (P < 0.001) and CA19-9 (P < 0.001). Combining the three markers was of independent prognostic value in CRC (HR = 2.532, 95% CI: 1.400-4.579, P = 0.002 for OS; and HR = 2.366, 95% CI: 1.334-4.196, P = 0.003 for DFS). Combined detection of preoperative serum CEA, CA19-9 and CA242 is of independent prognostic value for management of CRC patients treated surgically.     

Expression of blood group antigens H-2, Le(y), and sialylated-Le(a) in human colorectal carcinoma. An immunohistochemical study using double-labeling techniques.

In this study, double-labeling immunohistochemistry was used to gain insight into the coexpression or interrelationship between blood group antigens (BGA) that are differentiation antigens in the normal colon, and BGA that are sequential moieties in the same synthetic pathway. Paired-wise Sialylated-Le(a)/Le(y) and H-2/Le(y) was studied. The Sialylated-Le(a) and Le(y) are synthesized from type 1 and type 2 backbones, respectively. In the normal colon, the Le(y) and Sialylated-Le(a) are expressed by cells at the base and surface of the crypt, respectively, representing undifferentiated and differentiated enterocytes. The H-2 is considered oncofetal in nature, and is considered to be the immediate precursor in the synthesis of Le(y). In individual cancers. Sialylated-Lea and Le(y) were detected in different cancer cells within the same malignant glands, separately in different glands, and in different subcellular compartments of the same cell. Both H-2 and Le(y) were coexpressed in the same individual cells in 92% of cancers expressing both these BGA. In 50% of the cancers, the H-2 and Le(y) also were expressed separately in different malignant glands within individual tumors. These findings indicate that, in colorectal cancers, differentiation antigens (Sialylated Le(a) and Le(y)) are expressed by different individual cells within the same malignant gland somewhat, recapitulating the normal colon crypt. Antigens of different backbones occasionally may be expressed in the same cells but within different subcellular compartments. Precursor accumulation is common in cancers, and antigens in the same synthetic pathway are coexpressed in the same cell. The expression of H-2 and Le(y) in different glands (lack of coexpression) may be explained possibly by aberrant synthesis of Le(y) by an alternate pathway.     

卵巢癌患者调节性T细胞比率和肿瘤标志物CA125、CA19-9测定及临床意义

目的 探讨卵巢癌患者、卵巢良性疾病及健康成人女性调节性T细胞（Tregs）和肿瘤标志物CA125、CA19-9水平的差异,并将其与临床病理因素及预后进行相关分析。 方法 选择2016年10月~2017年10月承德医学院附属医院妇科收治的经病理确诊的卵巢癌患者43例,设为恶性组,另选择同期医院收治的卵巢良性疾病患者55例作为良性组,健康体检妇女50例作为对照组。比较3组患者Tregs和肿瘤标志物CA125、CA19 9在卵巢癌患者中的表达水平,分析其与临床病理因素及预后的关系。 结果 恶性组和良性组Tregs比例、CA125和CA19-9水平均高于对照组,恶性组Tregs比例、CA125和CA19-9水平高于良性组（P<0.05）。CA125、CA19-9、Tregs水平与患者的年龄差异无显著性（P>0.05）;CA125水平与卵巢癌患者的淋巴结是否转移、肿瘤分期和组织学类型均有关;Tregs表达水平与卵巢癌患者的淋巴结是否转移和肿瘤分期均相关,CA19-9水平只与肿瘤分期相关（P<0.05）。随访12个月后,Tregs-low组中位生存时间高于Tregs-high组（P<0.05）。卵巢癌中Tregs数与CA125存在显著正相关性（P<0.05）,而与CA19-9不具有相关性（P>0.05）。 结论 Tregs、CA125和CA19-9均可有望成为卵巢癌临床诊断、治疗和预后的指标。     

IL-6、IL-23、CEA和CA19-9在结直肠癌患者的血清学表达及意义

目的:探讨单独或联检血清IL-6、IL-23、CEA和CA19-9在结直肠癌诊断中的价值,分析它们与结直肠癌临床分期的关系.方法:分别检测75例结直肠癌患者、60例结直肠良性病变患者和58例健康者IL-6、IL-23、CEA和CA19-9血清水平,分析它们对结直肠癌诊断的临床价值及其与临床病理因素之间的关系.结果:结直...     

The human chromosome 19 linkage group FUT1 (H), FUT2 (SE), LE, LU, PEPD, C3, APOC2, D19S7 and D19S9

Families segregating for deficiency of the H α-2-L-fucosyltransferase, FUT1 , have been investigated for linkage between FUT1 and other markers on chromosome 19. The results provide evidence for close linkage between FUT1 and FUT2 and for looser linkage between FUT1 and APOG2 and between FUT1 and D19S7 . Pairwise linkage data are also reported between other markers investigated.     

血清CA125、CA19-9、CA72-4和EMA联检对卵巢癌的诊断价值

目的:探讨血清CA125、CA19-9、CA72-4和上皮膜抗原(EMA)联检对卵巢癌的诊断价值.方法:选择卵巢癌80例,正常对照50例,分别采用ELISA测定.结果:卵巢癌组血清CA125、CA19-9、CA72-4、EMA与对照组相比,两者具有明显差异(P＜0.05).卵巢癌组血清CA125、CA19-9、CA72-4和EMA单测阳性率分别为62.5%、50.0%、38.8%、75.0%,联检阳性率为97.5%.结论:血清CA125、CA19-9、CA72-4和EMA联检可提高诊断阳性率,对卵巢癌的临床辅助诊断有一定价值.     

Expression of mucins (MUC1, MUC2, MUC5AC,and MUC6) and type 1 Lewis antigens in cases with and without Helicobacter pylori colonization in metaplastic glands of the human stomach

Dendritic cells (DCs) take up tumour-specific antigen and migrate to regional lymph nodes to generate anti-tumour immunity. Although DC infiltration within human tumour tissue has been reported, the subset distribution has not been fully investigated. This study used immunohistochemistry to investigate DC subset distribution in colorectal adenocarcinoma. DCs expressing CD83, which are considered to be mature DCs, were present mainly in the invasive margin of cancer stroma. CD83(+) DCs in the invasive margin formed clusters with lymphocytes, the majority of which were CD45RO(+) T cells. The number of CD4(+) T cells was greater than that of CD8(+) T cells in these DC-lymphocyte clusters. The elongated cytoplasmic processes of CD83(+) DCs engulfed CD4(+) T cells. DCs that express CD1a were located throughout tumour tissue. Although the number of CD1a(+) DCs was almost the same as that of CD83(+) DCs in the invasive margin of cancer stroma, CD1a(+) DCs were mostly scattered and rarely formed clusters with lymphocytes. DCs that expressed both CD1a and CD83 were rare. Moreover, about 20% of lymphocytes in DC-lymphocyte clusters were positive for Ki-67, and CD83(+) DCs were attached to Ki-67(+) cells. CD83(+) DCs were also present in T-cell areas that had a distinctive structure involving the presence of B-cell lymphoid follicles. These results suggest that in the invasive margin of the colorectal cancer stroma, mature CD83(+) DCs form clusters with T cells to promote T-cell activation for the generation of tumour-specific immunity.     

Expression of trefoil peptides (TFF1, TFF2, and TFF3) in gastric carcinomas,intestinal metaplasia,and non-neoplastic gastric tissues

Trefoil factor family (TFF) domain peptides consist of three members that play a role in intestinal mucosal defence and repair, and in tumourigenesis. The role of the three TFF members in the gastric carcinogenesis cascade remains poorly defined. This study examined seven gastric cell lines, 50 gastric cancers and their adjacent non-cancer tissues, and tissues from 40 non-cancer patients, in order to elucidate the chronology of TFF expression in various stages of gastric carcinogenesis. TFF expression was determined by RT-PCR, immunohistochemistry, and western blot. Aberrant expression of TFF1, TFF2, and TFF3 was frequently detected in gastric cell lines. Specifically, TFF1 was detected in all non-cancer patients, but was detected in only 50% of gastric cancer and 66% of adjacent normal tissues. TFF2 expression was demonstrated in 87.5% of non-cancer patients, 34% of gastric carcinomas, and 58% of adjacent non-cancer tissues. There was a significant correlation between TFF1 and TFF2 expression in gastric cancer and adjacent non-cancer tissues (p<0.001). By contrast, TFF3 was detected in 25% of non-cancer patients and showed a predilection for areas with intestinal metaplasia (p=0.005). Sixty-two per cent of gastric cancers and 24% of neighbouring non-cancer tissues showed TFF3 expression. Immunoreactivity against TFF3 was demonstrated in goblet cells of intestinal metaplasia and within the cytoplasm and nuclei of tumour cells. Progressive loss of TFF1 and TFF2, together with the induction of TFF3, is likely to be involved in the early stage of the multi-step gastric carcinogenesis pathway.     

SET-CAN, the product of the t(9;9) in acute undifferentiated leukemia, causes expansion of early hematopoietic progenitors and hyperproliferation of stomach mucosa in transgenic mice

Leukemia-specific chromosome translocations involving the nucleoporin CAN/NUP214 lead to expression of different fusion genes including DEK-CAN, CAN-ABL, and SET-CAN. DEK-CAN and CAN-ABL1 are associated with acute myeloid leukemia and T-cell acute lymphoblastic leukemia, respectively, whereas SET-CAN was identified in a patient with acute undifferentiated leukemia. In addition, SET is overexpressed in solid tumors of the breast, uterus, stomach, and rectum. Ectopic expression of SET-CAN inhibits vitamin-D(3)-induced differentiation of the human promonocytic U937cells, whereas ectopic SET expression induces differentiation. Here, we assessed the leukemogenic potential of SET-CAN in the hematopoietic system of transgenic mice. Although SET-CAN mice showed expansion of an early progenitor cell pool and partial depletion of lymphocytes, the animals were not leukemia-prone and did not show shortening of disease latency after retroviral tagging. This suggests that SET-CAN expression in acute undifferentiated leukemia might determine the primitive phenotype of the disease, whereas secondary genetic lesions are necessary for disease development. Surprisingly, SET-CAN mice developed spontaneous hyperplasia of the stomach mucosa, which coincided with overexpression of beta-catenin and vastly increased numbers of proliferating gastric mucosa cells, suggesting a role of SET-CAN in proliferation of certain epithelial cells.