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ORIGINAL ARTICLE
Year : 2016  |  Volume : 12  |  Issue : 8  |  Page : 281-283

MutL homolog 1 expression in thyroid carcinoma and its clinical significance


Department of General Surgery, School of Medicine, Suzhou Kowloon Hospital Affiliated with Shanghai Jiao Tong University, Suzhou, Jiangsu, P.R. China

Date of Web Publication22-Feb-2017

Correspondence Address:
Yi Lu
Department of General Surgery, School of Medicine, Suzhou Kowloon Hospital Affiliated with Shanghai Jiao Tong University, Suzhou, Jiangsu 215021
P.R. China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.200764

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 > Abstract 

Objective: The aim of this study was to evaluate the MutL homolog 1 (MLH1) protein expression in thyroid cancer patients and its association with clinical pathological characteristics.
Materials and Methods: Forty thyroid cancer tissues and 22 partial paired normal thyroid tissues from 40 thyroid cancer patients who received surgery were collected in this study. MLH1 protein expression was tested by immunohistochemical method for the 40 cancer tissues and 22 partial paired normal thyroid tissues. The positive expression rate of MLH1 was compared between cancer tissue and normal tissue. The association between clinical pathological features such as gender, age, pathology type, clinical stage, lymph node metastasis, and MLH1 protein expression was calculated.
Results: MLH1 protein was mainly expressed in the nucleus with a small amount of expression in cytoplasm. The MLH1-positive expression rates in cancer and normal tissue were 47.5% and 81.8%, respectively, with statistical difference (P = 0.008); MLH1 protein positive expression was correlated with clinical stage (P = 0.04) and cancer lymph node metastasis (P = 0.03). However, its expression was not associated with gender (P = 0.63), age (P = 0.77), and pathology type (P = 0.77).
Conclusion: MLH1-negative expression may play an important role in thyroid cancer tissue development and lymph node metastasis.

Keywords: Clinical pathology features, expression, MutL homolog 1 gene, thyroid carcinoma


How to cite this article:
Lu Y, Jiang B, Yuan Y, Fei J, Wang J. MutL homolog 1 expression in thyroid carcinoma and its clinical significance. J Can Res Ther 2016;12:281-3

How to cite this URL:
Lu Y, Jiang B, Yuan Y, Fei J, Wang J. MutL homolog 1 expression in thyroid carcinoma and its clinical significance. J Can Res Ther [serial online] 2016 [cited 2017 Aug 19];12:281-3. Available from: http://www.cancerjournal.net/text.asp?2016/12/8/281/200764


 > Introduction Top


Thyroid carcinoma is a kind of malignant carcinoma that originating from follicular or parafollicular thyroid cells.[1] It is one of the most diagnosed types of endocrine cancer. The incidence rate of thyroid carcinoma has been significantly increased in the past three decades.[2] Moreover, it was believed that thyroid cancer is the fastest growing number of new cancer cases in women. MutL homolog 1 (MLH1) gene was located on chromosome 3 which mediates protein–protein interactions during mismatch recognition, strand discrimination, and strand removal. Defects in MLH1 are associated with the microsatellite instability (MSI) observed in hereditary nonpolyposis colon cancer.[3] MLH1 expression in thyroid cancer and its association with patients clinical pathological features has rarely reported. In this study, we collected 40 thyroid cancer tissues and 22 partial paired normal thyroid tissues from 40 thyroid cancer patients who received surgery and tested the MLH1 protein expression to evaluate the correlation between clinical pathological features and its expression.


 > Materials and Methods Top


Patients selection

Forty thyroid cancer tissues and 22 partial paired normal thyroid tissues from 40 thyroid cancer patients who received surgery were retrospectively collected from January 2013 to February 2016 in our hospital. The patients inclusion criteria were (1) pathology- or cytology-confirmed thyroid carcinoma, (2) without preoperation treatment, and (3) complete clinical data; exclusion criteria were (1) thyroid cancer without pathology confirmation, (2) with other malignant tumors, and (3) received preoperation treatment. Of the included 40 patients, there were 28 females and 12 males with the mean age of 36.8 ± 1.4 years.

Main reagents and instruments

MLH1 monoclonal antibody purchased from the United States Santa Cruz Company; ELISA Kit purchased from Shanghai Heng Fei Biological Technology Co. Ltd.; Microtome purchased from German Leica Inc.; and microscope purchased from Olympus, Japan.

Immunohistochemical assay

(1) Baking sheet at a temperature of 65°C; (2) paraffin wax; (3) antigen repair; (4) removal of peroxidase; (5) adding FIST antibody with incubation 1 h; (6) rinsing the sheet with distilled water for 2 min; (7) adding poly peroxidase anti-mouse/rabbit IgG with incubation at 37°C for 0.5 h; (8) DAB coloring; (9) microscopic examination.

Statistical analysis

All the analyses were performed using SPSS 16.0 software (http://www-01.ibm.com). Count data were expressed by rate and compared by Chi-square test or Fisher's exact test; P < 0.05 was considered statistically significant.


 > Results Top


MutL homolog 1 protein expression in cancer and normal thyroid tissue

MLH1 protein was mainly expressed in nucleus with a small amount of expression in cytoplasm [Figure 1]. The MLH1-positive expression rates in cancer and normal tissue were 47.5% and 81.8%, respectively, with statistical difference (P = 0.008) [Table 1].
Figure 1: MutL homolog 1 expression in thyroid cancer and normal thyroid tissue. (MutL homolog 1 positive expression [a] and negative expression [b] in thyroid cancer tissue; MutL homolog 1 positive expression [c] and negative expression [d] in normal thyroid tissue)

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Table 1: MutL homolog 1-positive expression rate in cancer and normal tissue of thyroid cancer patients

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MutL homolog 1 expression and clinical pathological characteristics

MLH1 protein positive expression was correlated with clinical stage (P = 0.04) and cancer lymph node metastasis (P = 0.03). However, its expression was not associated with gender (P = 0.63), age (P = 0.77), and pathology type (P = 0.77) [Table 2].
Table 2: Association between MutL homolog 1 expression and clinical pathology features in thyroid cancer patients

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 > Discussion Top


Thyroid carcinoma is one of the most common malignant tumors in head and neck. Although the incidence of thyroid cancer is only 5% of all the thyroid nodules and 1% of all the solid malignant carcinoma,[4] it is the most common malignant tumor in the endocrine system.[5] The incidence of thyroid cancer is all on the rise for the past three decades. However, the reason for the increased incidence of thyroid cancer is not clear. In addition, most of the epidemiology studies believe that thyroid cancer is complicated disease that involved genetic background and acquired environmental factors.[6],[7] The genetic background included malignant tumor history and genetic susceptibility. The acquired factors include ionizing radiation and abnormal uptake of iodine.[8],[9] The prognosis of thyroid cancer is well for early stage patients who received surgery treatment. However, for patients with advanced or metastasis disease, the prognosis was relative poor.

MLH1 gene was located on chromosome 3 which mediates protein–protein interactions during mismatch recognition, strand discrimination, and strand removal. Defects in MLH1 are associated with the MSI observed in hereditary nonpolyposis colon cancer.[10],[11],[12] MLH1 expression in thyroid cancer and its association with patients' clinical pathological features has rarely reported. In this study, we collected forty thyroid cancer tissues and 22 partial paired normal thyroid tissues from 40 thyroid cancer patients who received surgery and tested the MLH1 protein expression to evaluate the correlation between clinical pathological features and its expression. We found that MLH1 protein was mainly expressed in the nucleus with a small amount of expression in cytoplasm. The MLH1-positive expression rates in cancer and normal tissue were 47.5% and 81.8%, respectively, with statistical difference (P = 0.008); the low expression in cancer tissue may involve the thyroid cancer development. On further analysis, we found that MLH1 protein positive expression was correlated with clinical stage (P = 0.04) and cancer lymph node metastasis (P = 0.03). The MLH1-positive expression rate in early stage and nonmetastasis patients was much higher than that of late stage and metastasis disease. Hence, MLH1-negative expression may play an important role in thyroid cancer tissue development and lymph node metastasis.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
 > References Top

1.
Fagin JA, Wells SA Jr. Biologic and clinical perspectives on thyroid cancer. N Engl J Med 2016;375:1054-67.  Back to cited text no. 1
    
2.
Vigneri R, Malandrino P, Vigneri P. The changing epidemiology of thyroid cancer: Why is incidence increasing? Curr Opin Oncol 2015;27:1-7.  Back to cited text no. 2
    
3.
Niv Y. Microsatellite instability and MLH1 promoter hypermethylation in colorectal cancer. World J Gastroenterol 2007;13:1767-9.  Back to cited text no. 3
    
4.
Sipos JA, Mazzaferri EL. Thyroid cancer epidemiology and prognostic variables. Clin Oncol (R Coll Radiol) 2010;22:395-404.  Back to cited text no. 4
    
5.
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin 2016;66:7-30.  Back to cited text no. 5
    
6.
Asif F, Ahmad MR, Majid A. Risk factors for thyroid cancer in females using a logit model in Lahore, Pakistan. Asian Pac J Cancer Prev 2015;16:6243-7.  Back to cited text no. 6
    
7.
Wang P, Lv L, Qi F, Qiu F. Increased risk of papillary thyroid cancer related to hormonal factors in women. Tumour Biol 2015;36:5127-32.  Back to cited text no. 7
    
8.
Stansifer KJ, Guynan JF, Wachal BM, Smith RB. Modifiable risk factors and thyroid cancer. Otolaryngol Head Neck Surg 2015;152:432-7.  Back to cited text no. 8
    
9.
Lence-Anta JJ, Xhaard C, Ortiz RM, Kassim H, Pereda CM, Turcios S, et al. Environmental, lifestyle, and anthropometric risk factors for differentiated thyroid cancer in Cuba: A case-control study. Eur Thyroid J 2014;3:189-96.  Back to cited text no. 9
    
10.
Hegde M, Blazo M, Chong B, Prior T, Richards C. Assay validation for identification of hereditary nonpolyposis colon cancer-causing mutations in mismatch repair genes MLH1, MSH2, and MSH6. J Mol Diagn 2005;7:525-34.  Back to cited text no. 10
    
11.
Wahlberg SS, Schmeits J, Thomas G, Loda M, Garber J, Syngal S, et al. Evaluation of microsatellite instability and immunohistochemistry for the prediction of germ-line MSH2 and MLH1 mutations in hereditary nonpolyposis colon cancer families. Cancer Res 2002;62:3485-92.  Back to cited text no. 11
    
12.
Nyström-Lahti M, Perrera C, Räschle M, Panyushkina-Seiler E, Marra G, Curci A, et al. Functional analysis of MLH1 mutations linked to hereditary nonpolyposis colon cancer. Genes Chromosomes Cancer 2002;33:160-7.  Back to cited text no. 12
    


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    Tables

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