The Role Of S100A14 And LOXl2 In The Metastasis Of Highly Aggressive Papillary Thyroid Carcinoma

Papillary thyroid carcinoma is the most common malignant tumor of thyroid.Although local lymph node metastasis is easy to occur,most of them have a good prognosis through surgical treatment.However,previous studies have shown that highly aggressive variants papillary thyroid carcinoma has higher rate of lymph node metastasis and even has the possibility of distant metastasis.S100A14 and LOXL2 reported in colorectal cancer,cholangiocarcinoma,cervical carcinoma,ovarian cacinoma,breast carcinoma have been proved to play some roles in the proliferation,aggression and metastasis of obstetrics and gynecology tumors and digestive tract tumors,and the study of them in thyroid is rarely reported,which need to be further discussed.To collect clinical data and pathological sections of 753 cases diagnosed as papillary thyroid carcinoma in our hospital(Department of Pathology,Air Force Medical Center of PLA)in recent 6 years.According to the 2017 edition of WHO endocrine organ tumor classification standards,papillary thyroid carcinoma was divided into 15 pathological variants,of which the highly aggressive variants include tall cell variant of papillary thyroid carcinoma(TCVPTC),columnar cell variant of papillary thyroid carcinoma(CCVPTC),solid/trabecular variant of papillary thyroid carcinoma(SVPTC),hobnail variant of papillary thyroid carcinoma(HVPTC),diffuse sclerosis variant of papillary thyroid carcinoma(DSVPTC).The 753 cases of tissue sections were reviewed,and the clinical pathological characteristics of each variants were analyzed.Meanwhile 30 cases with highly aggressive pathological variants 30 cases of classic papillary thyroid carcinoma(CPTC)were randomly selected,and 30 cases of nodular goiter were included.A total of 90 cases of thyroid lesions tissue were made into tissue microarray.The expression of S100A14 and LOXL2 proteins in 30 cases of nodular goiter(NG group),30 cases of classic papillary thyroid carcinoma(CPTC group)and 30 cases of highly aggressive papillary thyroid carcinoma(highly aggressive group)were detected by immunohistochemistry.The relationship between S100A14 and LOXL2 expression and clinical pathological characteristics of PTC was discussed.Meanwhile,51 cases were detected q RT-PCR m RNA relative content expression.The ratio of male to female in 753 patients was 1:2.49,the age range was 17～75 years,and there were significant differences in sex distribution in the different groups.These included 562 CPTC patients,89 FVPTC patients,23 TCVPTC patients,22 SVPTC patients,20 CCVPTC patients,10 ECVPTC patients,8 CLCVPTC patients,7 HVPTC patients,5 OVPTC patients,4 cases of WLVPTC patients,3 cases of DSVPTC patients.Columnar cell variant,tall cell variant,solid/trabucular variant,hobnail variant out-of-gland aggression rate is higher than the classic variants,the difference is statistically significant.The rate of lymph node metastasis of PTC with hobnail variant composition and tall cell variants composition was higher than that of pure classic PTC,and the difference was statistically significant.S100A14 and LOXL2 are generally highly expressed in PTC tissue.And in the nodular goiter to the highly aggressive papillary thyroid carcinoma tissue expression showed a gradual increasing trend.And in the CPTC group and the highly aggressive group positive expression rate is statistically significant(P<0.05).The expression of S100A14 was positively associated with the expression of LOXL2 in PTC(r=0.032).The expression of LOXL2 m RNA in three groups of thyroid lesions showed a slow upward trend.Compared with the three groups,the relative expression of that of nodular goiter group.The difference was statistically significant(P<0.05),and there was no significant difference between other groups.The increasing trend of S100A14 m RNA in each group was not obvious.The relative expression of m RNA in highly aggressive group was significantly higher than that in other two groups(P<0.05).The relative expression of lymph node matastasis in highly aggressive group was higher than that in CPTC group(P<0.05).Therefor,the variants of CCVPTC,TCVPTC,HVPTC,DSVPTC and SVPTC are five pathological variants with highly aggressive behavior,compared with the classic variant and have a higher rate of extrathyroid extention and lymph node metastasis.High expression of S100A14 and LOXL2 may be related to poor biological behavior and invasiveity of PTC,while S100A14 may promote lymph node metastasis.This study suggests that S100A14 and LOXL2 may be markers of aggression and metastasis of papillary thyroid carcinoma,and may provide theoretical basis for targeted therapy of highly aggressive papillary thyroid carcinoma.