Indefinite for non-invasive neoplasia lesions in gastric intestinal metaplasia: the immunophenotype

Cassaro, Mauro; Rugge, Massimo; Tieppo, C.; Giacomelli, Luciano; Velo, Daniela; Nitti, Donato; Farinati, Fabio

doi:10.1136/jcp.2006.040386

Cited by 29 publications

(20 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The results showed that Ab 3 (NCL-L-hTERT antibody) was not absorbed any more with the nucleolin peptide than were the other anti-hTERT antibodies. In agreement with other researchers (27,70,71,(88)(89)(90)(91)(92)(93)(94)(95)(96)(97) and despite the objection raised by Wu et al (64) the Ab 3 proved suitable for hTERT detection. Mitsuishi et al (98) not only confirmed the consideration of Wu et al (64), but also found excellent correlation between nucleolin expression and telomerase activity levels in Bowens's disease and in normal sunexposed skin.…”

Section: Comparison Of Htert Results In Basal Cell Carcinomas and Squsupporting

confidence: 76%

Localization of telomerase hTERT protein in frozen sections of basal cell carcinomas (BCC) and tumor margin tissues

Fabricius

Kruse-Boitschenko²,

Khoury³

et al. 2009

Int J Oncol

View full text Add to dashboard Cite

Abstract.In previous studies we demonstrated telomerase activity in frozen tissues from BCC and their tumor-free margins by the PCR ELISA. In this study we examined in the same frozen sections immunohistochemical presence of hTERT in the nucleus. After fixation in acetone and methanol followed by steaming we used for visualization the antigenantibody reactions by APAAP. This was the best method of preparation of the frozen sections in our preliminary hTERT-study with squamous cell carcinomas. This study was supplemented with antibodies against Ki-67, nucleolin, common leucocyte antigen CD45 and mutated p53. The immunoreactive scores were determined and included the comparison with telomerase activity. The investigation of hTERT expression was performed in the tissues of 41 patients with BCC and control tissues of 14 patients without tumor. Eleven commercial antibodies were used for a nuclear staining of hTERT expression. With the anti-hTERT antibodies we looked for both satisfactory distribution and intensity of immunohistochemical labeling in the carcinomas and in the squamous epithelia of the tumor centers, of the tumor-free margins and of the control tissues. The hTERT expression in the BCC was distributed heterogeneously. The score values established by the anti-hTERT antibodies used were variably or significantly increased. In the stroma they tended to be negative, so we disregarded stroma hTERT. Proof of hTERT did not differ uniformly from telomerase activity. We compared the high with the lower median hTERT values in the Kaplan-Meier curve. Patients with lower hTERT scores in the center or tumor margin as shown by some of the antibodies suffered relapse earlier. Finally, we compared the hTERT expression in BCC tissues with the hTERT scores in HNSCC tissues from our previous study. Only one anti-hTERT antibody (our Ab 7) yielded significantly higher scores in BCC than in HNSCC.

show abstract

Section: Comparison Of Htert Results In Basal Cell Carcinomas and Squsupporting

confidence: 76%

Localization of telomerase hTERT protein in frozen sections of basal cell carcinomas (BCC) and tumor margin tissues

Fabricius

Kruse-Boitschenko²,

Khoury³

et al. 2009

Int J Oncol

View full text Add to dashboard Cite

show abstract

“…Among the 50 tested genes, TP53 was the best candidate as a diagnostic and prognostic biomarker of gastric epithelia transformation from dysplasia to early invasive cancer. Previous studies demonstrated loss of heterozygosis at the TP53 locus in 14 % of a series of gastric intestinal metaplasia and in 22 % of gastric dysplastic lesions [17]. In our series, 6 of 9 EGC-coexisting HG-IEN lesions were TP53 mutated, and p53 overexpression increased with the increasing severity of the precancerous lesion in an independent set of 75 biopsy specimens.…”

Section: Discussionmentioning

confidence: 47%

“…Moreover, most of the limited amount of material obtained from upper GI endoscopy is required for histopathological characterization of the specimen. As a result, there is still no molecular marker used in clinical practice to distinguish HG-IEN from early invasive neoplasia [17][18][19][20].…”

Section: Discussionmentioning

confidence: 99%

High-throughput mutation profiling identifies novel molecular dysregulation in high-grade intraepithelial neoplasia and early gastric cancers

et al. 2013

View full text Add to dashboard Cite

Background There is still no widely accepted molecular marker available to distinguish between gastric high-grade intraepithelial neoplasia (HG-IEN) and invasive early gastric cancer (EGC). Methods HG-IEN and EGC lesions coexisting in the same patient were manually microdissected from a series of 15 gastrectomies for EGC; 40 ng DNA was used for multiplex PCR amplification using the Ion AmpliSeq Cancer Panel, which explores the mutational status of hotspot regions in 50 cancer-associated genes. Results Of the 15 EGCs, 12 presented at least one somatic mutation among the 50 investigated genes, and 6 of these showed multiple driver gene somatic mutations. TP53 mutations were observed in 9 cases; APC mutations were identified in 3 cases; and ATM and STK11 were mutated in 2 cases. Seven HG-IEN lesions shared an identical mutational profile with the EGC from the same patient; 13 mutations observed in APC, ATM, FGFR3, PIK3CA, RB1, STK11, and TP53 genes were shared by both HG-IEN and ECG lesions. CDKN2A, IDH2, MET, and RET mutations were observed only in EGC. TP53 deregulation was further investigated in an independent series of 75 biopsies corresponding to all the phenotypic lesions occurring in the EGC carcinogenetic cascade. p53 nuclear immunoreaction progressively increased along with the dedifferentiation of the lesions (P \ 0.001). Overall, 18 of 20 p53-positive lesions showed a TP53 mutated gene. Discussion Our results support the molecular similarity between HG-IEN and EGC and suggest a relevant role for TP53 in the progression to the invasive phenotype and the use of immunohistochemistry as a surrogate to detect TP53 gene mutations.

show abstract

“…Xiao et al (106) conclude from their studies on culture cells and tissues fixated in formalin that chicken IgG antibodies can have definite advantages over the commonly used mammal IgG antibodies and exhibit less non-specific staining. Irrespective of the afore-mentioned objections, many authors continue to use the monoclonal NCL-L-hTERT for immunohistochemical proof of hTERT (63,66,(107)(108)(109)(110)(111)(112).…”

Section: Cells Which May Be Responsible For Telomerase Activity Outsimentioning

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

View full text Add to dashboard Cite

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.

show abstract

Indefinite for non-invasive neoplasia lesions in gastric intestinal metaplasia: the immunophenotype

Cited by 29 publications

References 29 publications

Localization of telomerase hTERT protein in frozen sections of basal cell carcinomas (BCC) and tumor margin tissues

Localization of telomerase hTERT protein in frozen sections of basal cell carcinomas (BCC) and tumor margin tissues

High-throughput mutation profiling identifies novel molecular dysregulation in high-grade intraepithelial neoplasia and early gastric cancers

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

Contact Info

Product

Resources

About