Quantification of telomerase activity of regions unstained with iodine solution that surround oral squamous cell carcinoma

Yajima, Yasutomo; Noma, Hiroyasu; Furuya, Yoko; Nomura, Takeshi; Yamauchi, Tomonori; Kasahara, Kiyohiro; Hatada, Kenichi; Takano, Masayuki

doi:10.1016/j.oraloncology.2003.08.017

Cited by 22 publications

(17 citation statements)

References 12 publications

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“…Yajima et al reported that telomerase activity was significantly different between iodine-stained areas of normal epithelium and -unstained areas of epithelial dysplasia (17). In another study, p53 expression in iodine-unstained areas was markedly higher than in iodine-stained areas (14).…”

Section: Discussionmentioning

confidence: 93%

Histopathological evaluation including cytokeratin 13 and Ki-67 in the border between Lugol-stained and -unstained areas

Ohta

Ogawa²,

Ono³

et al. 2010

Oncol Rep

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Abstract. Lugol's iodine staining (Lugol-staining) has been widely used to detect malignant changes in the cervix uteri and esophagus. However, pathological and histochemical changes in the border between Lugol-stained and -unstained areas in oral epithelial dysplastia and malignant lesions are not well understood. We examined the histological appearance of 20 cases of epithelial dysplasia surrounding squamous cell carcinoma using HE and PAS staining in the borders between Lugol-stained and -unstained areas. Subsequently, differences in the expression of cytokeratin 13 (CK13), an epithelium differentiation marker, and Ki-67, a cell proliferative marker, in those areas were investigated by immunohistochemistry. Lugol-stained areas of all cases showed mild dysplasia or normal epithelium appearance, while Lugol-unstained areas in most cases were diagnosed as moderate/severe dysplasia and carcinoma in situ. PAS reactions were limited or not found in the Lugol-unstained areas as compared to intense positivity in Lugol-stained areas. CK13 and Ki-67 protein expression was significantly different between Lugol-stained and -unstained areas. It was confirmed that epithelia showing precancerous or cancerous features were detected as Lugol-unstained boundary areas. A reduction in glycogen production caused by alterations of cell differentiation and proliferation associated with malignant changes may result in a lack of Lugol-staining.

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Section: Discussionmentioning

confidence: 93%

Histopathological evaluation including cytokeratin 13 and Ki-67 in the border between Lugol-stained and -unstained areas

Ohta

Ogawa²,

Ono³

et al. 2010

Oncol Rep

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“…2 and Table V) (93) of carcinoma-free tumor margin tissues some of which were dysplastic. In the present study we found positive telomerase values (13)(14)(15) in 52% of the tumor margin and 30% of the tumor distant tissues of patients with squamous cell carcinomas.…”

Section: Cells Which May Be Responsible For Telomerase Activity Outsimentioning

confidence: 99%

“…In this process it can bind with hTERT, with significant consequences for its nucleolar localization. (10,93) demonstrated telomerase in carcinoma-free tumor margins in head and neck tumors and addressed the question of whether the presence of telomerase activation occurs by lymphocytic infiltration in the tissue or whether it was an expression of field cancerization (1,2) in the region surrounding the tumor. In previous examinations we had demonstrated a limited correlation between telomerase activity and lymphocyte infiltration in tumor margin tissues (13,14,94,95).…”

Section: Correlation Of Htert Score Values and Telomerase Activity Inmentioning

confidence: 99%

Immunohistochemical determination of the appropriate anti-hTERT antibodies for in situ detection of telomerase activity in frozen sections of head and neck squamous cell carcinomas and tumor margin tissues

Fabricius

Kruse-Boitschenko²,

Khoury³

et al. 2009

Int J Oncol

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Abstract.In previous studies we demonstrated telomerase activity in frozen tissue from head and neck squamous cell carcinoma (HNSCC) and their tumor-free tumor margins. In the present study frozen sections from the same tissues were examined for in situ presence of hTERT. In preliminary investigations we established that the most suitable method of tissue preparation was fixation in acetone and methanol followed by steaming and visualization by APAAP. Most of the assays involved eleven anti-hTERT antibodies and were supplemented with the inclusion of antibodies Ki-67, antinucleolin and CD45. hTERT expression was investigated in the tissues of 61 patients with HNSCC and 37 patients without tumor. Semi-quantitative immunoreactive scores were correlated with telomerase activity. We examined the prognostic significance of hTERT expression with Kaplan-Meier curves and tested the immunological specificity of the antibodies by immunoabsorption with two hTERT peptides and a nucleolin peptide. Nuclear staining of satisfactory distribution and intensity was achieved in seven anti-hTERT antibodies both in the carcinomas and in the squamous epithelia of the tumor resection margins and in the control tissues. Proof of hTERT did not differ from telomerase activity. The telomerase activity demonstrated in tumor-free resection margins and in control tissues did, however, correlate with lymphocytic-monocytic infiltration (CD45 expression). This telomerase activity might be related to nuclear hTERT expression in the squamous epithelium, given that the hTERT score values in the connective tissue tended to be negative. The prognostic significance of hTERT expression demonstrated on paraffin sections from different tumor localizations was not confirmed for the frozen sections of patients with HNSCC. The hTERT specificity of the monoclonal NCL-L-hTERT, whose use as an antibody against hTERT has been questioned, was reexamined with immunohistochemical methods, but the intensity of its immunoabsorption with the nucleolin peptide did not exceed that observed in the other anti-hTERT antibodies.

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“…Lugol’s iodine visualisation of dysplastic mucosa is employed in management of oesophageal disease [4-8]. There is, however, a very limited literature describing the use of Lugol’s iodine in the management of head and neck mucosal neoplasia and there are no reported clinical trials [8-10]. …”

Section: Introductionmentioning

confidence: 99%

LIHNCS - Lugol’s iodine in head and neck cancer surgery: a multicentre, randomised controlled trial assessing the effectiveness of Lugol’s iodine to assist excision of moderate dysplasia, severe dysplasia and carcinoma in situ at mucosal resection margins of oral and oropharyngeal squamous cell carcinoma: study protocol for a randomised controlled trial

McCaul

Cymerman

Hislop

et al. 2013

Trials

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BackgroundOral cavity and oropharynx cancer are increasing in incidence worldwide but survival outcomes have not significantly improved over the last three decades. The presence of dysplasia or carcinoma in situ at surgical margins following resection of squamous carcinoma of the mucosal surfaces of the head and neck has been shown to be associated with a higher incidence of local recurrence and reduced survival. While invasive carcinoma in mucosal surfaces can usually be distinguished from adjacent normal mucous membrane, pre-malignant disease is much less readily distinguished at operation. We describe a protocol for a randomised, controlled trial in which we will assess the effectiveness of Lugol’s iodine staining in allowing visualisation and excision of cancer margin dysplasia at time of primary surgery.Methods/DesignWe will recruit 300 patients diagnosed with oral cavity or oropharynx squamous cell carcinoma. All participants will be planned for primary surgery with curative intent. After completion of baseline assessment participants will be randomised into either a standard surgical treatment arm or surgical treatment including Lugol’s iodine staining.DiscussionThis paper describes the rationale and design of a unique trial in head and neck surgical oncology. If margin dysplasia visualisation with Lugol’s iodine allows complete excision of high-risk, pre-cancer mucosa at time of primary surgery, this may lead to a reduction in local recurrence and improved survival.Trial registrationCurrent Controlled Trials ISRCTN03712770.

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Quantification of telomerase activity of regions unstained with iodine solution that surround oral squamous cell carcinoma

Cited by 22 publications

References 12 publications

Histopathological evaluation including cytokeratin 13 and Ki-67 in the border between Lugol-stained and -unstained areas

Histopathological evaluation including cytokeratin 13 and Ki-67 in the border between Lugol-stained and -unstained areas

Immunohistochemical determination of the appropriate anti-hTERT antibodies for in situ detection of telomerase activity in frozen sections of head and neck squamous cell carcinomas and tumor margin tissues

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