Progenitor stem cell marker expression by pulmonary carcinomas

Moreira, André L.; Gönen, Mithat; Rekhtman, Natasha; Downey, Robert J.

doi:10.1038/modpathol.2010.68

Cited by 54 publications

(42 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Several other studies agree with the observation that p63 is consistently positive in pulmonary squamous cell carcinoma, 16,20,29,31 and is a highly stable marker irrespective of the grade of differentiation. 19 It is possible that rare tumors reported as p63-negative squamous cell carcinoma in some studies represent a solid variant of adenocarcinoma.…”

Section: Discussionsupporting

confidence: 76%

Immunohistochemical algorithm for differentiation of lung adenocarcinoma and squamous cell carcinoma based on large series of whole-tissue sections with validation in small specimens

et al. 2011

Self Cite

View full text Add to dashboard Cite

Immunohistochemistry is increasingly utilized to differentiate lung adenocarcinoma and squamous cell carcinoma. However, detailed analysis of coexpression profiles of commonly used markers in large series of whole-tissue sections is lacking. Furthermore, the optimal diagnostic algorithm, particularly the minimalmarker combination, is not firmly established. We therefore studied whole-tissue sections of resected adenocarcinoma and squamous cell carcinoma (n ¼ 315) with markers commonly used to identify adenocarcinoma (TTF-1) and squamous cell carcinoma (p63, CK5/6, 34bE12), and prospectively validated the devised algorithm in morphologically unclassifiable small biopsy/cytology specimens (n ¼ 38). Analysis of whole-tissue sections showed that squamous cell carcinoma had a highly consistent immunoprofile (TTF-1-negative and p63/CK5/6/34bE12-diffuse) with only rare variation. In contrast, adenocarcinoma showed significant immunoheterogenetity for all 'squamous markers' (p63 (32%), CK5/6 (18%), 34bE12 (82%)) and TTF-1 (89%). As a single marker, only diffuse TTF-1 was specific for adenocarcinoma whereas none of the 'squamous markers,' even if diffuse, were entirely specific for squamous cell carcinoma. In contrast, coexpression profiles of TTF-1/p63 had only minimal overlap between adenocarcinoma and squamous cell carcinoma, and there was no overlap if CK5/6 was added as a third marker. An algorithm was devised in which TTF-1/p63 were used as the first-line panel, and CK5/6 was added for rare indeterminate cases. Prospective validation of this algorithm in small specimens showed 100% accuracy of adenocarcinoma vs squamous cell carcinoma prediction as determined by subsequent resection. In conclusion, although reactivity for 'squamous markers' is common in lung adenocarcinoma, a two-marker panel of TTF-1/p63 is sufficient for subtyping of the majority of tumors as adenocarcinomas vs squamous cell carcinoma, and addition of CK5/6 is needed in only a small subset of cases. This simple algorithm achieves excellent accuracy in small specimens while conserving the tissue for potential predictive marker testing, which is now an essential consideration in advanced lung cancer specimens. Modern Pathology (2011Pathology ( ) 24, 1348Pathology ( -1359 doi:10.1038/modpathol.2011; published online 27 May 2011Keywords: adenocarcinoma; CK5/6; p63; squamous cell carcinoma; TTF-1; 34bE12Adenocarcinoma and squamous cell carcinoma are the two major subtypes of non-small cell lung carcinoma. Until recently, therapeutic approaches to non-small cell lung carcinoma were largely guided by tumor stage, and there was no difference in treatment for adenocarcinoma vs squamous cell carcinoma. This monolithic approach to non-small cell lung carcinoma has dramatically changed in the last few years as a result of three major advances in thoracic medical oncology for advanced disease. These include (1) EGFR-targeted therapies, erlotinib

show abstract

Section: Discussionsupporting

confidence: 76%

Immunohistochemical algorithm for differentiation of lung adenocarcinoma and squamous cell carcinoma based on large series of whole-tissue sections with validation in small specimens

et al. 2011

Self Cite

View full text Add to dashboard Cite

show abstract

“…by guest www.bloodjournal.org From lung cancers, and 45% of squamous cell carcinoma, the differential expression being significant between the histologic subtypes (P ϭ .008). 34 Small cell carcinoma is an aggressive tumor that has been reported to express the stem cell markers podocalyxin-like protein 1 and Bmi-1, 35 whereas Moreira et al 34 found diffuse expression for all the stem cell markers they investigated (KIT, p63, CD133, MSI1, and MSI2) in small cell carcinoma, the other subtypes showing only focal or isolated positivity. It is of interest, therefore, that MSI2 and KIT were both expressed at high levels in small cell carcinoma, which the reports of Moreira et al 34 and Koch et al 35 indicate a more "stem-like" phenotype than the non-small cell subtypes.…”

Section: Msi2 Protein Predicts Unfavorable Outcome In Aml 2865mentioning

confidence: 99%

“…34 Small cell carcinoma is an aggressive tumor that has been reported to express the stem cell markers podocalyxin-like protein 1 and Bmi-1, 35 whereas Moreira et al 34 found diffuse expression for all the stem cell markers they investigated (KIT, p63, CD133, MSI1, and MSI2) in small cell carcinoma, the other subtypes showing only focal or isolated positivity. It is of interest, therefore, that MSI2 and KIT were both expressed at high levels in small cell carcinoma, which the reports of Moreira et al 34 and Koch et al 35 indicate a more "stem-like" phenotype than the non-small cell subtypes. Concordant with the hypothesis that MSI2 is preferentially expressed in stem cells, or cells with "stemness," is the finding of it in occasional paratrabecular sheets because myeloid differentiation normally proceeds from the paratrabecular niche into the intertrabecular space.…”

Section: Msi2 Protein Predicts Unfavorable Outcome In Aml 2865mentioning

confidence: 99%

“…[30][31][32][33] There are to date no reports of association of MSI2 with these markers, although Moreira et al reported high protein expression of MSI2, measured by immunohistochemistry, in association with KIT in pulmonary small cell carcinoma, 100% of which were positive for both these proteins. 34 In contrast, among cases of non-small cell pulmonary carcinoma, MSI2 was present in 25% of adenocarcinomas, 36% of large cell For each core, the entire core is shown (original magnification ϫ40) and a representative inset below (original magnification ϫ200). Micrographs were imaged using a Nikon Eclipse 80i microscope and captured using a Nikon DS-F digital camera with NIS-Elements D 3.1 software, with manipulation in CorelDRAW X3.…”

Section: Msi2 Protein Predicts Unfavorable Outcome In Aml 2863 Bloodmentioning

confidence: 99%

See 1 more Smart Citation

MSI2 protein expression predicts unfavorable outcome in acute myeloid leukemia

Byers

Currie

Tholouli

et al. 2011

Blood

View full text Add to dashboard Cite

show abstract

“…In addition, Oct4 was able to affect the cell biology of lung cancer cells by inducing cell proliferation, inhibiting apoptosis as well as promoting cell invasion and adhesion. Numerous clinical studies have examined the expression of Oct4 in lung cancer patients (18)(19)(20); however, the molecular mechanisms of its oncogenic role remain to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

Octamer-binding protein 4 affects the cell biology and phenotypic transition of lung cancer cells involving β-catenin/E-cadherin complex degradation

Chen

Ling

Yang-de

et al. 2014

Molecular Medicine Reports

View full text Add to dashboard Cite

Abstract. Clinical studies have reported evidence for the involvement of octamer-binding protein 4 (Oct4) in the tumorigenicity and progression of lung cancer; however, the role of Oct4 in lung cancer cell biology in vitro and its mechanism of action remain to be elucidated. Mortality among lung cancer patients is more frequently due to metastasis rather than their primary tumors. Epithelial-mesenchymal transition (EMT) is a prominent biological event for the induction of epithelial cancer metastasis. The aim of the present study was to investigate whether Oct4 had the capacity to induce lung cancer cell metastasis via the promoting the EMT in vitro. Moreover, the effect of Oct4 on the β-catenin/E-cadherin complex, associated with EMT, was examined using immunofluorescence and immunoprecipitation assays as well as western blot analysis. The results demonstrated that Oct4 enhanced cell invasion and adhesion accompanied by the downregulation of epithelial marker cytokeratin, and upregulation of the mesenchymal markers vimentin and N-cadherin. Furthermore, Oct4 induced EMT of lung cancer cells by promoting β-catenin/E-cadherin complex degradation and regulating nuclear localization of β-catenin. In conclusion, the present study indicated that Oct4 affected the cell biology of lung cancer cells in vitro through promoting lung cancer cell metastasis via EMT; in addition, the results suggested that the association and degradation of the β-catenin/E-cadherin complex was regulated by Oct4 during the process of EMT. IntroductionLung cancer is one of the most prevalent types of malignant tumor worldwide, with a five-year survival rate of ~16% (1). Mortality among lung cancer patients is more frequently due to metastasis rather than their primary tumors. Therefore, it is necessary to elucidate the molecular mechanisms of lung cancer metastasis in order to develop effective treatment options.Epithelial-mesenchymal transition (EMT) is a process characterized by downregulation of epithelial markers and upregulation of mesenchymal markers (2,3). Previous studies have proposed that EMT may be a key step in the progression of tumor cell metastasis (4-6).Octamer-binding protein 4 (Oct4), a transcription factor that belongs to the Pit-Oct-Unc (POU) family, has been reported to be a master regulator of maintenance and differentiation in pluripotent cells. It has been suggested that Oct4 may be a key component of the regulation of self-renewal and differentiation in stem cells (7-9); in addition, Oct4 may also have a crucial role in cancer development (10). Chen et al (11) demonstrated that Oct4 expression was involved in the tumorigenesis and malignancy of lung cancer. The aims of the present study were to investigate the effect of Oct4 on the cell biology of lung cancer cells in vitro, elucidate the underlying mechanisms associated with lung cancer metastasis and examine the effect of Oct4 on the degradation of the β-catenin/E-cadherin complex degradation, a process strongly associated with EMT. Materials and methods Cell

show abstract

Progenitor stem cell marker expression by pulmonary carcinomas

Cited by 54 publications

References 44 publications

Immunohistochemical algorithm for differentiation of lung adenocarcinoma and squamous cell carcinoma based on large series of whole-tissue sections with validation in small specimens

Immunohistochemical algorithm for differentiation of lung adenocarcinoma and squamous cell carcinoma based on large series of whole-tissue sections with validation in small specimens

MSI2 protein expression predicts unfavorable outcome in acute myeloid leukemia

Octamer-binding protein 4 affects the cell biology and phenotypic transition of lung cancer cells involving β-catenin/E-cadherin complex degradation

Contact Info

Product

Resources

About