Immunohistochemical study of MUC1 mucin in premalignant oral lesions and oral squamous cell carcinoma

Nitta, T.; Sugihara, Kazumasa; Tsuyama, Shinichro; Murata, Fusayoshi

doi:10.1002/(sici)1097-0142(20000115)88:2<245::aid-cncr1>3.0.co;2-t

Cited by 54 publications

(59 citation statements)

References 32 publications

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“…MVD has been reported to be correlated with regional recurrence in T 1-3 N 0 oral cavity squamous cell carcinoma (12). MUC1 is a mucin-like glycoprotein encoded by the MUC1 gene and has been reported to be correlated with lymph node metastasis in oral squamous cell carcinoma (13). COX-2 has been found to be up-regulated in head and neck carcinoma (14) and has been shown to increase tumor metastasis potential (15).…”

Section: Introductionmentioning

confidence: 99%

Predictive Markers for Late Cervical Metastasis in Stage I and II Invasive Squamous Cell Carcinoma of the Oral Tongue

Lim

Zhang

Ishii

et al. 2004

Clinical Cancer Research

241

200

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Purpose: Patients with oral tongue carcinoma treated by intraoral excision only should be followed up carefully for cervical lymph node metastasis and salvaged immediately if found, because some patients have a more aggressive clinical course. The purpose of this study was to find useful markers for predicting late cervical metastasis in patients with stage I and II invasive squamous cell carcinoma of the oral tongue.Experimental Design: We investigated clinicopathologic factors and immunohistochemical biomarkers predicting late cervical metastasis in surgical specimens from 56 patients with T 1-2 N 0 M 0 invasive squamous cell carcinoma of the oral tongue who did not undergo elective neck dissection. Histopathologic factors including tumor thickness, mode of invasion, Broders grade, total score of three different malignancy grading systems, eight other clinicopathologic parameters, and immunohistochemical expression of p53, cyclin D1, Ki-67, epidermal growth factor receptor, microvessel density, cyclooxygenase-2, MUC1, laminin-5 ␥2, E-cadherin, and ␤-catenin were examined. All of the clinicopathologic factors and immunohistochemical expression of biomarkers were compared in terms of survival.Results: In the univariate analysis, tumor thickness (P ‫؍‬ 0.009), Broders grade (P ‫؍‬ 0.017), nest shape (P ‫؍‬ 0.005), mode of invasion (P < 0.001), Anneroth score (P ‫؍‬ 0.029), Bryne score (P < 0.001), and E-cadherin expression (P ‫؍‬ 0.003) were correlated with late cervical metastasis. Multivariate analysis on late cervical metastasis revealed that tumor thickness >4 mm, mode of invasion grade 3 or 4, and E-cadherin expression were independent factors. Late cervical metastasis was the only prognostic factor for overall survival (P ‫؍‬ 0.002).Conclusions: Our results indicate that patients with stage I and II invasive squamous cell carcinoma of the oral tongue with tumor thickness >4 mm, mode of invasion grade 3 or 4, and low expression of E-cadherin should be considered a high-risk group for late cervical metastasis when a wait-and-see policy for the neck is adopted.

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Section: Introductionmentioning

confidence: 99%

Predictive Markers for Late Cervical Metastasis in Stage I and II Invasive Squamous Cell Carcinoma of the Oral Tongue

Lim

Zhang

Ishii

et al. 2004

Clinical Cancer Research

241

200

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“…During this process, loss of metastasis suppressor gene(s) function should be a crucial step in the progression of cancer cells from a nonmetastatic to a metastatic phenotype. Recent studies have identified the correlation between gene expression patterns and lymph node metastasis in OSCC (2,3). Yet, there is no critical determinant that can be used to identify which primary lesions will develop into metastatic OSCC.…”

Section: Introductionmentioning

confidence: 99%

Lin-7C/VELI3/MALS-3: An Essential Component in Metastasis of Human Squamous Cell Carcinoma

Onda

Uzawa

Nakashima³

et al. 2007

Cancer Research

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Using proteomic selection, functional verification, and clinical validation, we identified specific down-regulation of Lin-7C/ VELI3/MALS-3 (Lin-7C), which marks oral squamous cell carcinoma (OSCC) metastasis. Despite a rarity of sequence variations in the Lin-7C gene in both primary OSCC and OSCCderived cells, a high prevalence of hypermethylation was detected in the CpG island region that strongly correlated with its down-regulation. Inducible Lin-7C mRNA by experimental demethylation was found in all OSCC cells tested. Overexpression of the Lin-7C gene in an OSCC cell clone does not contribute to underproliferation but results in a noninvasive phenotype with elevated b-catenin expression. Experimental metastases in multiple organs of immunodeficient mice were inhibited in cells expressing Lin-7C. Finally, the Lin-7C expression status in primary tumors afforded significantly (P < 0.001) high accuracy for predicting lymph node metastasis. These results establish Lin-7C as a novel target of early detection, prevention, and therapy for OSCC metastasis.

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“…It has previously been noted that autoimmune responses to cancer-specific antigens such as MUC1 and cyclin B1 can be identified in healthy donor populations; therefore, we decided to further characterize humoral immune function in CLL patients. [18][19][20] Although the majority of CLL patients maintained detectable LCP1-specific IgG, only 6 of 12 were able to mount an identifiable IgG response to the vaccinated (Table 1). (E) ELISA analysis of LCP1-specific IgG in 33 previously untreated CLL patients and 6 healthy donor controls.…”

Section: Mass Spectroscopy Of Autoimmune Igg Responses Identifies Lcpmentioning

confidence: 99%

Lymphocyte cytosolic protein 1 is a chronic lymphocytic leukemia membrane-associated antigen critical to niche homing

Dubovsky¹,

Chappell²,

Harrington³

et al. 2013

Blood

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• The authors developed a novel method for isolating tumor membrane antigens.• LCP1 is functionally relevant to leukemia chemokine induced migration.Membrane antigens are critical to the pathogenesis of chronic lymphocytic leukemia (CLL) as they facilitate microenvironment homing, proliferation, and survival. Targeting the CLL membrane and associated signaling patterns is a current focus of therapeutic development. Many tumor membrane targets are simultaneously targeted by humoral immunity, thus forming recognizable immunoglobulin responses. We sought to use this immune response to identify novel membrane-associated targets for CLL. Using a novel strategy, we interrogated CLL membrane-specific autologous immunoglobulin G reactivity. Our analysis unveiled lymphocyte cytosolic protein 1 (LCP1), a lymphocyte-specific target that is highly expressed in CLL. LCP1 plays a critical role in B-cell biology by crosslinking F-actin filaments, thereby solidifying cytoskeletal structures and providing a scaffold for critical signaling pathways. Small interfering RNA knockdown of LCP1 blocked migration toward CXCL12 in transwell assays and to bone marrow in an in vivo xenotransplant model, confirming a role for LCP1 in leukemia migration. Furthermore, we demonstrate that the Bruton's tyrosine kinase inhibitor ibrutinib or the PI3K inhibitor idelalisib block B-cell receptor induced activation of LCP1. Our data demonstrate a novel strategy to identify cancer membrane target antigens using humoral anti-tumor immunity. In addition, we identify LCP1 as a membrane-associated target in CLL with confirmed pathogenic significance. This clinical trial was registered at clinicaltrials.gov; study ID number: OSU-0025 OSU-0156. (Blood. 2013;122(19):3308-3316)

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Immunohistochemical study of MUC1 mucin in premalignant oral lesions and oral squamous cell carcinoma

Cited by 54 publications

References 32 publications

Predictive Markers for Late Cervical Metastasis in Stage I and II Invasive Squamous Cell Carcinoma of the Oral Tongue

Predictive Markers for Late Cervical Metastasis in Stage I and II Invasive Squamous Cell Carcinoma of the Oral Tongue

Lin-7C/VELI3/MALS-3: An Essential Component in Metastasis of Human Squamous Cell Carcinoma

Lymphocyte cytosolic protein 1 is a chronic lymphocytic leukemia membrane-associated antigen critical to niche homing

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