Expression of MUC1 in esophageal squamous-cell carcinoma and its relationship with prognosis of patients from Linzhou city, a high incidence area of northern China

Song, Zibo; Gao, Shanshan; Yi, Xiao; Li, Yanjie; Wang, Qiming; Zhuang, Ze-Hao; Wang, Lidong

doi:10.3748/wjg.v9.i3.404

Cited by 27 publications

(27 citation statements)

References 25 publications

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“…The expression of MUC‐1 by malignant cells is an important step in tumor cell spread and metastasis. MUC‐1 inhibits the E‐cadherin‐mediated cell‐cell adhesion system,40 and its expression is correlated with poor prognosis in patients with lung carcinoma28 and other malignancies 41–43. In the current study, expression of MUC‐1 did not show any correlation with survival or the incidence of skip metastases.…”

Section: Discussioncontrasting

confidence: 59%

Skip metastasis in nonsmall cell lung carcinoma

Prenzel

Baldus

Mönig

et al. 2004

Cancer

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BACKGROUND Skip metastasis to mediastinal lymph nodes is a prognostic factor for patients with nonsmall cell lung carcinoma (NSCLC). Little is known about the biologic behavior of tumors with noncontinuous spread to the mediastinal lymph nodes. In patients with pN2 skip metastases, micrometastases to N1 lymph nodes, which only mimic skip metastases, have not been investigated. METHODS In a retrospective study, the authors analyzed the primary tumor specimens from 45 patients with pN2 NSCLC (18 patients had squamous cell carcinomas, 23 had adenocarcinomas, and 4 had large cell carcinomas). They immunohistochemically evaluated the expression of p21, p53, MUC‐1, Bcl‐2, c‐ErbB‐2, and E‐cadherin. Survival rates and biomarker expression levels were compared between patients with pN2 disease and infiltration of N1 lymph nodes (without skip metastasis [n = 28]) and patients with pN2 disease without N1 infiltration (with skip metastasis [n = 17]). To evaluate micrometastasis in the pN1 lymph nodes of 17 patients with skip metastases, lymph nodes were stained using the anticytokeratin antibody, AE1/AE3. RESULTS The 5‐year survival rate of patients with skip metastases was 41%, compared with 14% for patients without skip metastases (P = 0.019). In a multivariate analysis, the incidence of skip metastases did not vary significantly according to gender, age, histology, pT status, or cM status. Three skip‐positive patients (17.6%) had micrometastatic tumor involvement of pN1 lymph nodes. After adding these patients to the group of patients without skip metastases, there was still a significant difference in survival between the two groups. p53, MUC‐1, c‐ErbB‐2, and E‐cadherin expression levels in primary tumor specimens were not significantly different in patients with continuous metastasis and patients with skip metastases. Patients with skip metastases expressed lower levels of p21 (P = 0.026), whereas Bcl‐2 expression levels were considerably higher (P = 0.019) compared with the corresponding levels in patients without skip metastases. CONCLUSIONS Patients with NSCLC and pN2 skip metastases have a more favorable prognosis than do patients with pN2 disease without skip metastases. Tumor specimens from these patients exhibit elevated expression of the antiapoptosis gene BCL2 and lower expression levels of p21 relative to patients with pN2 disease without skip metastases. Micrometastases occurred in 3 of 17 (17.6%) patients with pN2 disease and skip metastases diagnosed by routine histopathology. Cancer 2004. © 2004 American Cancer Society.

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Section: Discussioncontrasting

confidence: 59%

Skip metastasis in nonsmall cell lung carcinoma

Prenzel

Baldus

Mönig

et al. 2004

Cancer

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“…17 However, the mechanism in which manner MUC1 promotes ESCC metastasis remains unknown. In the present study, we demonstrate co-overexpression of MUC1 and MMP13 in ESCC patients, especially in patients with lymph node metastasis.…”

Section: Muc1 Induces Metastasis In Esccmentioning

confidence: 99%

MUC1 induces metastasis in esophageal squamous cell carcinoma by upregulating matrix metalloproteinase 13

Zheng

Liao

et al. 2011

Laboratory Investigation

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Esophagus squamous cell carcinoma (ESCC) is one of the most deadly malignances because of its high frequency of metastasis. Given the associations of MUC1 with ESCC and tumor metastasis, we explored a potential role of MUC1 in ESCC metastasis. Among 40 ESCC and 20 paired normal tissue specimens examined, we found a significant increase of MUC1 expression in ESCC and more importantly, that expression of MUC1 and MMP13 are strongly correlated in patients who had lymph node metastasis. Studies with cell models indicated that overexpression of MUC1 upregulates the expression of MMP13, leading to increased cell migration. In support of a mode of transcriptional regulation, promoter analysis revealed that MUC1 stimulates MMP13 expression through the Runx-2-binding site. The link of MUC1 to cell motility was further confirmed by the finding that depletion of MUC1 resulted in reduced expression of MMP13 and cell migration, invasion and adhesion. Moreover, the loss of cell metastatic potential was rescued by overexpression of MMP13 completely. Collectively, our findings indicate that MUC1 contributes to ESCC metastasis by stimulating MMP13 expression, suggesting MUC1 as a novel diagnostic biomarker and therapeutic target in ESCC. Esophageal squamous cell carcinoma (ESCC) frequently exhibits extensive local invasion or regional lymph node metastasis at the time of initial diagnosis; therefore, it is one of the most common aggressive diseases with poor outcome. 1 Tumor invasion and metastasis involve degradation of different components of the extracellular matrix and require the actions of proteolytic enzymes, such as matrix metalloproteinases (MMPs), which are produced either by the tumor cells or surrounding stromal cells.2,3 MMP13 is a highly regulated zinc-dependent endopeptidase and has been reported to be associated with vascular invasion and lymph node metastasis in ESCC. 4 Mechanisms involved in regulation of MMP13 in ESCC are likely complex and poorly understood.Mucins are high-molecular-weight glycoproteins that have been identified as markers of adverse prognosis and as attractive therapeutic targets.5 MUC1, one of transmembrane mucins, is normally expressed in esophageal epithelium.Patients with MUC1 high expression often appear with advanced stage or lymph node metastasis suggesting correlation of the MUC1 expression and the invasion or metastasis of ESCC.6 In this study, we investigated the expression of MUC1 and MMP13 in ESCC patients and the potential functional relationship in tumor metastasis and prognosis. MATERIALS AND METHODS Tissue Sample CollectionA total of 40 paraffin-embedded archival specimens of primary ESCC cases were enrolled in this study: 20 with lymph node metastasis and 20 without lymph node metastasis. A total of 20 paired normal esophageal tissue specimens distant from the cancerous lesion in patients without lymph node metastasis were used as control. These patients did not receive any preoperative adjuvant radiation or chemotherapy.

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“…However, MUC1 does not appear to be expressed in normal lymph nodes. [10][11][12] Thus, if MUC1 is detected in regional lymph nodes from patients with esophageal cancer, this could indicate lymph node metastasis. Reverse transcription-polymerase chain reaction (RT-PCR), a technique used to detect tissue-specifi c or tumor-specifi c mRNA from cancer cells, has recently been used in esophageal cancer studies, most of which provide supporting evidence that LNMM is associated with diminished relapse-free survival.…”

Section: Introductionmentioning

confidence: 99%