Aspectos histológicos, genéticos y moleculares de las lesiones preneoplásicas de la mucosa gástrica / Histological, genetic and molecular aspects of preneoplastic lesions of the gastric mucosa

Siendo el cáncer gástrico la 3ª causa de muerte por cáncer en Chile, y existiendo estrategias de tamizaje consistentes en pesquisa de lesiones preneoplásicas de la mucosa gástrica, es relevante conocer los aspectos genéticos y moleculares que puedan ser aplicados, en la optimización de dichas estrategias a grupos de mayor riesgo. El objetivo de este manuscrito fue revisar la evidencia actual en los aspectos señalados, y de la inmunohistoquímica de 4 marcadores (p53, CDX2, MUC2 y S100A9) en la mucosa gástrica normal y en las lesiones preneoplásicas de la misma.

SUMMARY: Since gastric cancer is the 3rd leading cause of death from cancer in Chile, and there are screening strategies consisting of screening for preneoplastic lesions of the gastric mucosa, it is important to know certain genetic and molecular aspects that can be applied in optimizing these strategies for higher risk groups. The aim of this manuscript was to review the current evidence on the aforementioned aspects, and on the immunohistochemistry of 4 markers (p53, CDX2, MUC2 and S100A9) in normal gastric mucosa and in its preneoplastic lesions.

Marcação imunoistoquímica de CDX2 e Ki67 no adenocarcinoma gástrico / CDX2 and Ki67 immunohistochemistry marking in gastric adenocarcinoma

Introdução: A proteína CDX2 é um fator de transcrição específico do intestino, que está presente no tecido gástrico apenas quando há uma metaplasia intestinal. A metaplasia intestinal é uma lesão precursora do adenocarcinoma gástrico. O Ki67 é um biomarcador de proliferação celular. Objetivo: Verificar a presença da proteína CDX2 no adenocarcinoma gástrico. Comparar a expressão da CDX2 entre os diferentes graus de diferenciação e entre os níveis de proliferação celular. Método: A partir de 62 blocos histológicos contendo amostras de adenocarcinoma gástricos (4 bem diferenciados, 30 moderadamente diferenciados e 28 pouco diferenciados), foi feita a construção de blocos multiamostrais (TMA). Procedeu-se a marcação imunoistoquímica com os anticorpos escolhidos e realizou-se a leitura da área positiva imunocoradas. Resultados: 31 amostras foram positivas para a CDX2 e 31 negativas, sem diferença significativa entres os graus de diferenciação (p = 0,576). 38 amostras foram classificadas como de baixo grau de proliferação celular e 24 como de alto grau. Não houve diferença estatística de grau de proliferação celular entre os graus de diferenciação (p = 0,676). O grau de proliferação celular variou dependendo da expressão da CDX2 (p = 0,036). Conclusão: A expressão da proteína CDX2 esteve presente em 50% dos adenocarcinomas gástricos. Não houve diferença estatística da expressão do CDX2 entres os graus de diferenciação do adenocarcinoma gástrico. A proliferação celular variou dependendo da expressão da CDX2, havendo um maior nível de proliferação celular nas amostras que apresentaram expressão positiva para CDX2

Background: CDX2 protein is an intestinal specific transcription factor that is present in the gastric tissue only when there is intestinal metaplasia. Intestinal metaplasia is a gastric adenocarcinoma precursor injury. Ki67 is a cell proliferation biomarker. Objective: Verify the presence of CDX2 protein in gastric adenocarcinoma. Compare the CDX2 expression between the differentiation degree groups and between the cell proliferation degrees. Methods: It was collected 62 paraffin blocks containing the gastric adenocarcinoma samples (4 well differentiated adenocarcinoma, 30 moderately differentiated and 28 poorly differentiated). It was made the tissue microarrays blocks (TMA), so it was proceeded to immunohistochemical staining with the anti-CDX2 and the anti-Ki67 antibodies and it was accomplished the read of the positive immune-stained area. Results: 31 samples were positive for CDX2 expression, and 31 were negative. There was no statistical difference of the CDX2 expression between the differentiation degree groups (p = 0.576). 38 samples were classified as low degree of cell proliferation and 24 as high degree. There was no statistical difference of the cell proliferation degree between the differentiation degree groups (p = 0.676). The degree of cell proliferation ranged depending on the CDX2 expression (p = 0.036). Conclusion: Protein CDX2 expression was observed in 50% of gastric adenocarcinoma samples. There was no statistical difference of the CDX2 expression between the differentiation degree groups. The cell proliferation ranged depending of CDX2 expression, with a higher index of cell proliferation in the positive CDX2 expression samples

Are cdx2, beta-catenin and wnt immunomarchers useful for evaluating the chance of disease progression or evolution to death in patients with colorectal cancer? / Os imunomarcadores cdx2, beta-catenina e wnt são úteis para avaliar a chance de progressão de doença ou a evolução para óbito em pacientes com câncer colorretal?

ABSTRACT Background: Colorectal cancer (CRC) is one of the most common types of cancer in the world. Over time, intestinal epithelial cells undergo mutations that may lead to proliferative advantage and the emergence of cancer. Mutations in the beta-catenin pathway are amongst those described in the development of CRC. Aim: To verify the existence of a relation between the presence of Wnt3, beta-catenin and CDX2 in colorectal cancer samples and clinical outcomes such as disease progression or death. Method: Wnt3a, beta-catenin and CDX2 immunohistochemistry was performed on CRC tissue microarray samples (n=122), and analysis regarding the relation between biomarker expression and disease progression or death was performed. Results: No significant difference was found between the presence or absence of CDX2, beta-catenin or Wnt3a expression and clinical stage, tumor grade, disease progression or death. Conclusion: CDX2, beta-catenin and Wnt3a are not useful to predict prognosis in patients with CRC.

RESUMO Racional: O câncer colorretal (CCR) é um dos tipos mais comuns no mundo. As células epiteliais intestinais podem sofrer mutações que ocasionam vantagem proliferativa e culminam com o surgimento do câncer. Mutações da via da beta-catenina foram descritas entre as que podem ocasioná-lo. Objetivo: Verificar a existência de relação entre a expressão de Wnt3, beta-catenina e CDX2 em amostras de câncer colorretal com os eventos clínicos progressão de doença e óbito. Método: Foi realizada análise imunoistoquímica de Wnt3a, beta-catenina e CDX2 em blocos multiamostrais de CRC (n=122), e avaliada a relação entre a expressão dos biomarcadores e os desfechos progressão de doença e óbito. Resultados: Não foram encontradas diferenças significativas entre a expressão ou ausência de CDX2, beta-catenina ou Wnt3a e estádio clínico, grau de diferenciação tumoral, presença de progressão de doença ou evolução ao óbito. Conclusão: Os marcadores CDX2, beta-catenina e Wnt3a não são úteis para predizer prognóstico em pacientes com CCR.

Intestinal mucinous adenocarcinoma with metastases to epididymis, testis and tunica albuginea in a dog

A case of intestinal mucinous adenocarcinoma with metastasis to gonadal tissue is reported. A 13-year-old, male, poodle dog presented with intestinal and peritoneal masses, as well as infiltrative masses in testicular tunics. Samples were biopsied and submitted for histopathological analysis. Microscopically, intestinal lesion consisted of an adenocarcinoma (mucinous type), with infiltration of muscular layers and mesenteric adipose tissue. In gonadal tissue, there was neoplastic infiltration of epididymis and tunica albuginea (with a predominantly tubular pattern), and testicular parenchyma (with a predominantly signet-ring cell pattern). Immunohistochemistry was positive for CDX2 and pancytokeratin, and negative for vimentin, supporting the diagnosis of intestinal mucinous adenocarcinoma with metastases to epididymis, testis and tunica albuginea.

CDX2 inhibits invasion and migration of gastric cancer cells by phosphatase and tensin homologue deleted from chromosome 10/Akt signaling pathway / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Gastric cancer (GC) is one of the most prevalent malignancies in the world today, with a high mortality rate. CDX2 is a Drosophila caudal-related homeobox transcription factor that plays an important role in GC. Phosphatase and tensin homologue deleted from chromosome 10 (PTEN) is an important tumor suppressor which is widely expressed in normal human tissues. The aim of the study was to determine the relationship and mechanism between CDX2 and PTEN in invasion and migration of GC cells.</p><p><b>METHODS</b>pcDNA3-CDX2 plasmids were transfected into MGC-803 cells to up-regulate CDX2 protein, and small interfering RNA-CDX2 was transfected to down-regulate CDX2. The influence of CDX2 or PTEN on cell migration and invasion was measured by invasion, migration and wound healing assays. Western blotting assay and immunofluorescence were used to detect the expression of CDX2, PTEN, phosphorylation of Akt, E-cadherin and N-cadherin. Statistical significance was determined by one-way analysis of variance.</p><p><b>RESULTS</b>The results showed that CDX2 reduced the migration and invasion of GC cells (P < 0.05), and inhibited the activity of Akt through down-regulating PTEN expression (P < 0.05). CDX2 also restrained epithelial-mesenchymal transition of GC cells.</p><p><b>CONCLUSIONS</b>CDX2 inhibited invasion and migration of GC cells by PTEN/Akt signaling pathway, and that may be used for potential therapeutic target.</p>

Expressions of CDX2 and β-catenin and their correlation in acute myeloid leukemia / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the expressions of CDX2 and β-catenin and their correlation in acute myeloid leukemia (AML).</p><p><b>METHODS</b>Real-time PCR was used to examine the expressions of CDX2 and β-catenin mRNA in 92 de novo AML and 30 non-malignant patients (control), and Western blot was employed to detect CDX2 and β-catenin protein expressions in 26 de novo AML and 8 non-malignant patients.</p><p><b>RESULTS</b>The positivity rates of CDX2 mRNA and protein expressions in AML group were 84.78% and 76.92%, respectively, but no CDX2 mRNA or protein expression were detected in control group (P<0.01). The expressions of β-catenin mRNA and protein were detected in all the patients in both groups but its expressions in AML group were significantly higher (P<0.01). The expressions of CDX2 and β-catenin mRNA were significantly correlated with WBC counts and LDH levels (P<0.01). The expression of CDX2 mRNA was not detected and the expression of β-catenin mRNA was decreased to normal level in AML patients with complete remission, while the expressions of CDX2 and β-catenin mRNA were increased again in those with disease relapse. There were significantly positive correlations between CDX2 and β-catenin expressions at both mRNA and protein levels (P<0.01).</p><p><b>CONCLUSION</b>Up-regulation of CDX2 gene and activation of Wnt/β-catenin pathway co-exist in AML patients and the expressions of CDX2 and β-catenin are positively correlated.</p>

CDX-2, MUC-2 and B-catenin as intestinal markers in pure mucinous carcinoma of the breast

BACKGROUND: Pure mucinous adenocarcinoma of the breast is a rare entity characterized by the production of variable amounts of mucin comprising 1% to 6% of breast carcinomas. Some mucinous adenocarcinomas have shown expression of intestinal differentiation markers such as MUC-2. This study examines the expression of intestinal differentiation markers in this type of breast carcinoma. RESULTS: Twenty-two cases of pure mucinous adenocarcinoma of the breast were assessed. Immunochemistry was performed for beta-catenin, CDX-2 and MUC-2. All cases were positive for B-catenin. MUC-2 positivity was observed in all cases; 63. 6% were 3 plus positive. All cases were negative for CDX-2. CONCLUSIONS: These results suggest that mucinous breast carcinomas express some markers of intestinal differentiation, such as MUC-2 and beta-catenin; however, future studies with a larger series of cases and using molecular techniques that help affirm these results are needed.

Clinicopathologic characteristics and histogenesis of mucinous tumor of peritoneum / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathologic characteristics, prognosis and histologic origin of the mucinous tumor of the peritoneum.</p><p><b>METHODS</b>According to 2010 WHO classification of tumours of the digestive system, 34 cases diagnosed as "pseudomyxoma peritonei (PMP) " were reevaluated and divided into low grade and high grade. Immunohistochemistry was applied to investigate the expression of SATB2 and the histologic origin of the mucinous tumor of the peritoneum, using antibodies against SATB2, CK7, CK20 and CDX-2. The relationship between clinicopathologic characteristics and prognosis of the low grade and high grade tumors were analyzed.</p><p><b>RESULTS</b>Twenty five patients had low grade mucinous tumors (two of them were no cell type), nine patients had high grade mucinous tumors. There was no significant difference between low grade and high grade mucinous tumors in age, sex, recurrence and organs involvement (P>0.05). Thirty patients were followed up, the overall survival rates of patients with low grade and high grade mucinous tumors were 13/21 (61.9%) and 3/9, respectively. The median survival time was 74 and 24 months in low and high grade patients, and the difference was statistically significant (P=0.002).Immunohistochemistry showed the expression rates of CDX-2, CK20, and CK7 in totally 32 cases (excluding 2 cases of no cell type) were 30/32(93.8%), 31/32 (96.9%), and 3/16, respectively; the expression rates of CDX-2, CK20, and CK7 in 16 cases with distinct primary site were 15, 16, and 1, respectively; fifteen of 16 cases of tumors of unknown primary site were positive for CDX-2 and CK20, two of the them were positive for CK7. There was no difference in the expression of CDX-2, CK20 and CK7 between tumors with distinct primary site and tumors with unknown primary site (P>0.05). The expression rate of SATB2 in the cases was 56.3% (18/32), excluding 2 cases of no cell type. There was no significant difference between low grade and high grade tumors in the expression of SATB2 [15/23(65.2%) vs 3/9, P=0.102], also SATB2 was not related to the prognosis of the tumor (P=0.786).</p><p><b>CONCLUSION</b>The prognosis of the mucinous tumor of the peritoneum was significantly different between low grade and high grade according to WHO 2010 classification, and most mucinous tumor of the peritoneum originated from the appendix.</p>

Morphological observation of human gastric cancer cell SGC-7901 clones and identification of gastric cancer stem cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To dynamically investigate the morphology of human gastric cancer SGC-7901 cell clones, and then compare the tumorigenic ability of different clones in order to identify the tumor stem cell clones.</p><p><b>METHODS</b>Clones derived from gastric cancer SGC-7901 cells were assessed by morphological observation, and the clone formation rate and proportion of each clone were calculated. The expression of CD44 and CDX2 in different clones was detected by immunofluorescence microscopy and Western blot. Furthermore, different clones were isolated and cultured, and their self-renewal property was assayed. Cells of different clones were subcutaneously inoculated into nude mice and the tumorigenic ability of each group was determined.</p><p><b>RESULTS</b>Clones derived from gastric cancer SGC-7901 cells had three types, i.e. clones of tight, transitional and loose types. The total clone formation rate was (9.80 ± 1.07)%, and the proportion of tight, transitional and loose type clones was 10.2%, 56.0% and 33.8%, respectively. The results of immunofluorescence microscopic examination showed that the signal of CD44 was significantly stronger in the tight clones than in the transitional and loose clones, however, the signal of CDX2 was weakest in the tight colonies. The results of Western blot were consistent with that of immunofluorescence microscopic observation. SGC-7901 cells of tight clones possessed strong ability of self-renewal and in vivo tumorigenicity in the nude mice.</p><p><b>CONCLUSION</b>SGC-7901 cell clones vary in morphology and differentiation, and the tight type clones may include rich gastric cancer stem cells.</p>

Expression level of CDX2 gene in acute myeloid leukemia and its clinical significance / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the expression and clinical significance of Caudal-type homeobox transcription factor 2 (CDX2) gene in acute myeloid leukemia (AML) patients.</p><p><b>METHOD</b>Real time quantitative PCR (RQ-PCR) was used to test the expression level of CDX2 gene in 108 de novo AML patients and the clinical features of these patients were analyzed.</p><p><b>RESULTS</b>CDX2 gene transcript levels were detectable in bone marrow mononuclear cells from 108 AML patients and 7 healthy donors, the median expression level were 1179.44 (range 14.15 - 867 961.10) and 105.30 (range 22.30 - 453.11). There was a statistically significant difference in expression level of CDX2 gene between the AML patients and normal donor (P < 0.01). All 14 patients with FLT3-ITD(+) were in CDX2 gene higher expression group (P = 0.018), including 10 patients with normal karyotype. In the 83 treated AML patients (P = 0.046) and 57 higher WBC count (≥ 10×10(9)/L, P = 0.048) patients, the higher expression level of CDX2 gene was associated with lower complete remission (CR) rates.</p><p><b>CONCLUSIONS</b>Higher expression level of CDX2 gene was seen mostly in AML patients with FLT3-ITD mutation and with lower CR rates. CDX2 gene might be a prognostic molecular marker in AML patients with normal karyotype.</p>

Expression of cdx2 gene in pediatric patients with leukemia and its clinical significance / 中国实验血液学杂志

This study was aimed to investigate the expression of cdx2 gene in pediatric patients with acute leukemia and its clinical implication. The bone marrow and peripheral blood were collected from 33 newly diagnosed pediatric patients with acute leukemia, the cdx2 gene expression in each AL subtypes and normal controls was detected by RT-PCR, the relationship between cdx2 expression and response to treatment was observed. The results showed that the expression of cdx2 was positive in 25 out of 30 AL cases (83.3%), to be exact, in 20 of 21 ALL cases (95.2%) and in 5 of 9 AML cases (55.6%), which showed statistical difference (p < 0.05). The cdx2 mRNA could be detected also in 1 of 3 CML cases. However, no expression of cdx2 was observed in all normal control which revealed significant difference between patient group and normal control group. 21 AL patients with cdx2 positive expression (17 ALL and 4 AML patients) and 4 AL patients with cxd2 negative expression (1 ALL and 3 AML patients) all reached complete remission (CR) after treatment, which showed no correlation with CR rate. 8 patients with positive cdx2 expression were followed up. As a result, the cdx2 positive expression at initial diagnosis of patients remained positive at reaching CR, but it gradually turned to negative along with prolonging of CR, while the cdx2 negative expression at initial diagnosis of patients remained negative at CR in bone marrow level. It is concluded that cdx2 positive expression is observed in the majority of pediatric AL patients, even positive rate in ALL patients is higher than that in AML patients, while the cdx2 expression also can be observed in CML patients. The cdx2 positive expression is not related to the CR rate in AL patients.

Expression and clinical significance of caudal type homeobox transcription factor-2 in adult acute lymphocytic leukemia / 中国实验血液学杂志

This study was aimed to investigate the expression and clinical significance of CDX1, CDX2 and CDX4 genes in acute lymphocytic leukemia (ALL). Expressions of CDX1, CDX2, and CDX4 in 51 adult acute lymphocytic leukemia patients and 14 healthy subjects were detected by reverse transcription polymerase chain reaction (RT-PCR). The results indicated that CDX1, CDX2 and CDX4 were not expressed in 14 healthy persons and 15 CR ALL patients, the positive expression rate of CDX2 gene in de novo ALL patients was 60.8%, while it obviously decreased in patients with complete remission (CR) (p < 0.05); the expression of CDX2 was increased again in relapsed patients (81.8%). When the expression of CDX2 was analyzed in different risk groups of ALL patients, the CDX2 expression rate in high risk (HR) patients was 91.7%, and that in the standard risk (SR) group was 45.7%. Furthermore, analyses of CDX1 and CDX4 expression in series of ALL samples did not show the expression of these genes. In patients with adult ALL at diagnosis and relapse, the CR rate of patients with CDX2 positive expression was lower than that of patients with CDX2 negative expression (p < 0.05). The median survival time in CDX2 positive expression patients was shorter than that in negative expression patient. It is concluded that expression of CDX2 may correlated with pathogenesis and relapse of adult ALL, but the expression of CDX1 and CDX4 don' t associated with pathogenesis and relapse of adult ALL; the CR rate and prognosis of patients with CDX2 positive expression is lower and poor. The expression of CDX2 may be used as a marker for occurrence, relapse and poor prognosis of adult ALL patients.

Clinicopathologic and immunohistochemical study on early gastric signet-ring cell carcinoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the expression of gastric and intestinal phenotypic markers in gastric signet-ring cell (SRC) carcinoma and the relationship with the clinicopathologic parameters and prognosis.</p><p><b>METHODS</b>Immunohistochemical study was carried out in 91 cases of early-stage SRC carcinoma using MUC1, MUC5AC and MUC6 antibodies as the gastric phenotypic markers and MUC2 and CDX2 antibodies as the intestinal phenotypic markers. According to the expression of phenotypic markers, the tumors were classified into three different subgroups: gastric, intestinal and mixed. The findings were analyzed together with various clinical parameters and follow-up data.</p><p><b>RESULTS</b>Amongst the 91 cases studied, 53 cases (58.2%) belonged to gastric type, 22 cases (24.2%) mixed type and 16 cases (17.6%) intestinal type. The positive rates of MUC2 and CDX2 in early submucosal carcinoma were significantly higher than those in mucosal carcinoma (P < 0.01). On the other hand, the rates of MUC5AC and MUC6 expression in early submucosal carcinoma were significantly lower than those in mucosal carcinoma (P < 0.01 and P < 0.05). The rates of MUC2 and CDX2 expression in cases with lymph node metastasis and vascular invasion were significantly higher than those in cases without nodal or vascular involvement (P < 0.05). The expression of CDX2 was also significantly higher in cases with larger tumor size (P < 0.05). Cases with intestinal phenotype more likely had invasion deeper than mucosal layer and carried higher chance of lymph node metastasis (P = 0.000 and P = 0.003). Intestinal and mixed types correlated with shortened five-year survival.</p><p><b>CONCLUSIONS</b>The intestinal type of SRC carcinoma is associated with poorer biologic behavior and prognosis, as compared with that of the gastric type. Classification on the basis of immunophenotypic markers may be useful in predicting prognosis and guiding treatment for patients with gastric SRC carcinoma.</p>

Significance of IL-1beta-induced ectopic expression of CDX2 in the intestinal metaplasia of gastric epithelium / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the effect of IL-1beta on the expression of CDX2 in human gastric epithelial cell line GES-1 and its role in the intestinal metaplasia.</p><p><b>METHODS</b>GES-1 cells were treated with IL-1beta in different concentrations and the expressions of CDX2 mRNA and protein were detected by real-time PCR, immunocytochemistry and Western blot at different time points. GES-1 cells were then pre-treated with NF-KappaB pathway inhibitor PDTC, and the expression of CDX2 mRNA and protein induced by IL-1beta were detected. The cell ultra-structure of GES-1 cells was observed by electronic microscope after GES-1 being treated with IL-1beta for 25 days.</p><p><b>RESULTS</b>Levels of CDX2 mRNA and protein were 0.0749 + or - 0.0021 and 0.56 + or - 0.04 in the cells treated with 1 microg/L IL-1beta(P<0.05). After pre-treatment with PDTC, levels of CDX2 mRNA and protein were 0.0006 + or - 0.0002 and 0.40 + or - 0.06(P<0.05). Some changes in the cell ultra-structure of GES-1 were found by electronic microscope when GES-1 was treated with IL-1beta for 25 days.</p><p><b>CONCLUSION</b>IL-1beta can stimulate CDX2 mRNA and protein expression in GES-1 cells through the NF-KappaB signal pathway, indicating that IL-1beta plays an important role in the intestinal metaplasia.</p>

Clinicopathological and immunohistochemical features of colorectal sessile serrated adenoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathological characteristics and expression status of Ki67, p53, CEA, CDX, CK7 in colorectal sessile serrated adenoma (SSA).</p><p><b>METHODS</b>The clinicopathological data of 11 cases of SSA, 51 cases of hyperplastic polyp (HP) and one case with mixed HP/SSA were reviewed and analyzed retrospectively. The expression of Ki67, p53, CEA, CDX and CK7 were detected by immunohistochemistry.</p><p><b>RESULTS</b>The major histological features in SSA were architectural abnormality in crypts, dilatation of serrated crypt bases like an inverted "T" or "L" shape adjacent to muscularis mucosa. Atypical cells containing round to oval nuclei and nucleoli were also observed. The immunohistochemical staining showed that the expression of p53 increased gradually from HP to TA: 11.8% in HP, 20.0% in SSA, 41.2% in VTA and 75.0% in TA, with a significant difference among the groups (chi(2) = 17.996, P = 0.000). However, no significant difference in the expression of CDX and CK7 was observed between HP and SSA. Of the 10 SSA cases, positive expression of Ki67 was found in cells located in the base or middle part of crypt in 6 cases, positive cells index was 26% - 50% in 5 cases, and > 50% in 3. Compared with the expression of Ki67 in the HP, VTA and VA, SSA showed a significant difference in both the positive cell number and in the positive regions. (positive number: chi(2) = 34.601, P = 0.000; positive regions: chi(2) = 63.077, P = 0.000).</p><p><b>CONCLUSION</b>Morphological diagnosis of SSA was mainly based on crypt architectural and cellular abnormalities, and the crypt architectural abnormality may be more important than cellular features. Detection of p53 and Ki67 expression may be helpful in differential diagnosis and understanding the nature of SSA.</p>

Expressions of homeobox transcription factor-2 and E-cadherin in gastric carcinoma and their clinical significance / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the expressions of homeobox transcription factor-2 (CDX(2)) and E-cadherin and their relations to the clinicopathological characteristics of gastric carcinoma.</p><p><b>METHODS</b>Immunohistochemistry was performed on 83 human gastric carcinoma specimens and 40 normal gastric mucosa specimens for examining the expressions of CDX(2) and E-cadherin, and the relations of their expression with the tumor differentiation, infiltration and metastasis were analyzed.</p><p><b>RESULTS</b>According to the LaurAn classification, the positive expression rate of CDX(2) in intestinal type of gastric carcinoma was 56.86%, and 34.38% in the diffuse type, showing significant difference between the two types (P<0.05). The positivity rate of E-cadherin was also significantly different between the two types (66.67% vs 28.13%, P<0.01). In regard to tumor differentiation, the positivity of CDX(2) and E-cadherin expressions was significantly different between moderately to well differentiated tumors and poorly differentiated ones (P<0.01). The tumors infiltrating mucosal and submucosal layers were significantly different from those infiltrating the muscular and serous membrane layer in the positivity of CDX(2) and E-cadherin expressions (P<0.01), which were also different for the presence of lymph node metastasis (P<0.05). Regression analysis did not reveal significant correlations between CDX(2) and E-cadherin expression in gastric carcinoma (P>0.05).</p><p><b>CONCLUSION</b>The abnormal expression of CDX(2) and E-cadherin plays an important role in the development of gastric carcinoma, especially the intestinal type. CDX(2) and E-cadherin may serve as useful markers to predict the prognosis of patients with gastric carcinoma.</p>

Role of CDX2 immunostaining in diagnosis of gastrointestinal adenocarcinoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the expression of CDX2 in normal and tumor tissues, and to evaluate the value of CDX2 immunostaining in the diagnosis of gastrointestinal adenocarcinoma.</p><p><b>METHOD</b>Seventy-six samples of normal tissue and 612 samples of tumor tissue were studied by tissue microarray technology and immunohistochemistry for CDX2.</p><p><b>RESULTS</b>CDX2 was strongly expressed in surface epithelium of 13 samples of normal intestine and in ductal epithelium of 8 samples of normal pancreas, as well as in 47 samples (92.2%) of colonic adenocarcinoma and 58 samples (66.9%) of gastric adenocarcinoma. As for other tumor types, there was only weak or patchy CDX2 positivity. The positivity rates were as follows: ovarian mucinous adenocarcinoma 15.6% (10/64), pancreatic cancer 33.3% (3/9), thyroid cancer 27.3% (3/11) and extrahepatic biliary cancer 25% (4/16). On the other hand, primary tumors of breast, prostate, kidney, adrenal and liver were negative for CDX2.</p><p><b>CONCLUSIONS</b>CDX2 is expressed mainly in normal epithelium of intestinal tract and small pancreatic ducts, as well as in primary adenocarcinoma of gastrointestinal tract. CDX2 may thus play an important role in distinguishing primary non-intestinal adenocarcinoma from metastatic adenocarcinoma of gastric or colorectal primary.</p>