Expressions of PTEN and Ki-67 in Primary Thyroid Cancer Tissues and Its Clinical Significances_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 LIUZhi-chun ,  ZHAOLiang

Department of General Surgery, The First People's Hospital of Tianshui City, Tianshui 741000, Gansu Province, China;

Corresponding author：

ZHAOLiang, Email: 253314468@qq.com

Keywords：

Thyroid cancer; PTEN; Ki-67; Immunohistochemistry; RT-PCR

DOI：

10.7507/1007-9424.20160345

Video：

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Objective To detect expressions of PTEN and Ki-67 in primary thyroid cancer tissues and explore its clinical significances. Methods The expressions of PTEN protein and Ki-67 protein in 40 cases of paraffin-embedded tissues of primary thyroid cancer and the corresponding paracancerous tissues were detected by immunohistochemical method. The expressions of PTEN mRNA and Ki-67 mRNA in 14 cases of resected fresh tissues of primary thyroid cancer and the corresponding paracancerous tissues were detected by RT-PCR method. The relations between clinicopathologic characteristics and expression of PTEN protein or Ki-67 protein in the primary thyroid cancer tissues were analyzed. Results ① The PTEN protein positive expression rate and the PTEN mRNA in the primary thyroid cancer tissues were significantly lower than those in the corresponding paracancerous tissues[35.0% (14/40) versus 60.0% (24/40), P<0.05; 0.225 7±0.036 3 versus 0.503 6±0.037 5, P<0.05], the Ki-67 protein positive expression rate and Ki-67 mRNA in the primary thyroid cancer tissues were significantly higher than those in the corresponding paracancerous tissues [72.5% (29/40) versus 42.5% (17/40), P<0.05; 1.212 1±0.042 1 versus 0.293 6±0.027 4, P<0.05]. ② The expressions of PTEN protein and Ki-67 protein were associated with the histological grading, pathological type, tumor stage, and presence of regional lymph node metastasis (P<0.05), which not associated with the patient's gender, age and integrity of tumor capsule or not (P>0.05). ③ The PTEN and Ki-67 protein expressions in the primary thyroid cancer tissues had a significantly negative correlation (r_s=-0.605, P=0.000), which in the corresponding paracancerous tissues had no correlation (r_s=-0.021, P=0.899). Conclusion PTEN and Ki-67 genes abnormally express in thyroid cancer tissue, which might be related with occurrence and development and its mechanism of primary thyroid cancer. Combination of two genes might contribute to identification of pathologic type, judge of biological behavior, and tumor stage of primary thyroid cancer, which might serve as a new target for diagnosis and treatment of it.

Citation： LIUZhi-chun, ZHAOLiang. Expressions of PTEN and Ki-67 in Primary Thyroid Cancer Tissues and Its Clinical Significances. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2016, 23(11): 1348-1352. doi: 10.7507/1007-9424.20160345 Copy

1.	敖小凤, 高志红. 甲状腺癌流行现状研究进展. 中国慢性病预防与控制, 2008, 16(2):217-219.
2.	宫汝梅. PTEN 表达下调对乳腺癌细胞生物学性状的影响. 山东大学, 2010.
3.	孙理. PTEN和HER-2/neu在上皮性卵巢癌组织中的表达及相关性. 实用肿瘤学杂志, 2008, 22(3):229-232.
4.	Smith JA, Sharma N, Nankivell P, et al. The presentation, natural history and outcome of T1a/b thyroid cancer with regard to new grading systems. Eur Arch Otorhinolaryngol, 2015, 272(2):439-444.
5.	Sakurada A, Suzuki A, Sato M, et al. Infrequent genetic alterations of the PTEN/MMAC1 gene in Japanese patients with primary cancers of the breast, lung, pancreas, kidney, and ovary. Jpn J Cancer Res, 1997, 88(11):1025-1028.
6.	Pires MM, Hopkins BD, Saal LH, et al. Alterations of EGFR, p53 and PTEN that mimic changes found in basal-like breast cancer promote transformation of human mammary epithelial cells. Cancer Biol Ther, 2013, 14(3):246-253.
7.	Steck PA, Pershouse MA, Jasser SA, et al. Identification of a candi-date tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat Genet, 1997, 15(4):356-362.
8.	Kurebayashi J, Kanomata N, Shimo T, et al. Marked lymphovascular invasion, progesterone receptor negativity, and high Ki67 labeling index predict poor outcome in breast cancer patients treated with endocrine therapy alone. Breast Cancer, 2014, 21(2):214-222.
9.	Phelan E, Kamani D, Shin J, et al. Neural monitored revision thyroid cancer surgery:surgical safety and thyroglobulin response. Otolary-ngol Head Neck Surg, 2013, 149(1):47-52.
10.	Konopka B, Janiec-Jankowska A, Czapczak D, et al. Molecular genetic defects in endometrial carcinomas:microsatellite instability, PTEN and beta-catenin (CTNNB1) genes mutations. J Cancer Res Clin Oncol, 2007, 133(6):361-371.
11.	Gerdes J, Lemke H, Baisch H, et al. Cell cycle analysis of a cell proli-feration-associated human nuclear antigen defined by the monoc-lonal antibody Ki-67. J Immunol, 1984, 133(4):1710-1715.
12.	Risinger JI, Hayes K, Maxwell GL, et al. PTEN mutation in endome-trial cancers is associated with favorable clinical and pathologic characteristics. Clin Cancer Res, 1998, 4(12):3005-3010.
13.	Saito M, Okamoto A, Kohno T, et al. Allelic imbalance and muta-tions of the PTEN gene in ovarian cancer. Int J Cancer, 2000, 85(2):160-165.
14.	Maehama T, Dixon JE. PTEN:a tumour suppressor that functions as a phospholipid phosphatase. Trends Cell Biol, 1999, 9(4):125-128.
15.	Vascellari M, Giantin M, Capello K, et al. Expression of Ki67, BCL-2, and COX-2 in canine cutaneous mast cell tumors:association with grading and prognosis. Vet Pathol, 2013, 50(1):110-121.
16.	Liaw D, Marsh DJ, Li J, et al. Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome. Nat Genet, 1997, 16(1):64-67.

1. 敖小凤, 高志红. 甲状腺癌流行现状研究进展. 中国慢性病预防与控制, 2008, 16(2):217-219.
2. 宫汝梅. PTEN 表达下调对乳腺癌细胞生物学性状的影响. 山东大学, 2010.
3. 孙理. PTEN和HER-2/neu在上皮性卵巢癌组织中的表达及相关性. 实用肿瘤学杂志, 2008, 22(3):229-232.
4. Smith JA, Sharma N, Nankivell P, et al. The presentation, natural history and outcome of T1a/b thyroid cancer with regard to new grading systems. Eur Arch Otorhinolaryngol, 2015, 272(2):439-444.
5. Sakurada A, Suzuki A, Sato M, et al. Infrequent genetic alterations of the PTEN/MMAC1 gene in Japanese patients with primary cancers of the breast, lung, pancreas, kidney, and ovary. Jpn J Cancer Res, 1997, 88(11):1025-1028.
6. Pires MM, Hopkins BD, Saal LH, et al. Alterations of EGFR, p53 and PTEN that mimic changes found in basal-like breast cancer promote transformation of human mammary epithelial cells. Cancer Biol Ther, 2013, 14(3):246-253.
7. Steck PA, Pershouse MA, Jasser SA, et al. Identification of a candi-date tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat Genet, 1997, 15(4):356-362.
8. Kurebayashi J, Kanomata N, Shimo T, et al. Marked lymphovascular invasion, progesterone receptor negativity, and high Ki67 labeling index predict poor outcome in breast cancer patients treated with endocrine therapy alone. Breast Cancer, 2014, 21(2):214-222.
9. Phelan E, Kamani D, Shin J, et al. Neural monitored revision thyroid cancer surgery:surgical safety and thyroglobulin response. Otolary-ngol Head Neck Surg, 2013, 149(1):47-52.
10. Konopka B, Janiec-Jankowska A, Czapczak D, et al. Molecular genetic defects in endometrial carcinomas:microsatellite instability, PTEN and beta-catenin (CTNNB1) genes mutations. J Cancer Res Clin Oncol, 2007, 133(6):361-371.
11. Gerdes J, Lemke H, Baisch H, et al. Cell cycle analysis of a cell proli-feration-associated human nuclear antigen defined by the monoc-lonal antibody Ki-67. J Immunol, 1984, 133(4):1710-1715.
12. Risinger JI, Hayes K, Maxwell GL, et al. PTEN mutation in endome-trial cancers is associated with favorable clinical and pathologic characteristics. Clin Cancer Res, 1998, 4(12):3005-3010.
13. Saito M, Okamoto A, Kohno T, et al. Allelic imbalance and muta-tions of the PTEN gene in ovarian cancer. Int J Cancer, 2000, 85(2):160-165.
14. Maehama T, Dixon JE. PTEN:a tumour suppressor that functions as a phospholipid phosphatase. Trends Cell Biol, 1999, 9(4):125-128.
15. Vascellari M, Giantin M, Capello K, et al. Expression of Ki67, BCL-2, and COX-2 in canine cutaneous mast cell tumors:association with grading and prognosis. Vet Pathol, 2013, 50(1):110-121.
16. Liaw D, Marsh DJ, Li J, et al. Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome. Nat Genet, 1997, 16(1):64-67.

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Expressions of PTEN and Ki-67 in Primary Thyroid Cancer Tissues and Its Clinical Significances

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