Immunohistochemical detection of XIAP and p63 in adenomatous hyperplasia, atypical adenomatous hyperplasia, bronchioloalveolar carcinoma and well-differentiated adenocarcinoma

Wu, Maoxin; Orta, Lurmag; Gil, Joan; Gan, Li; Hu, Alice; Burstein, David

doi:10.1038/modpathol.2008.5

Cited by 24 publications

(10 citation statements)

References 30 publications

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“…We hypothesize an origin from the basal reserve cells of the TRU that show positive immunostaining for TTF1 and p63, overlapping with the results obtained in our 10 cases of PD-NSCLC. This hypothesis has been previously suggested by Wu et al [12], limited to previously called "brochiolo-alveolar carcinomas" and "well-differentiated adenocarcinomas (WD-ADC)", but not for PD-NSCLC. Moreover, TTF-1 was not assessed in their study.…”

Section: Discussionmentioning

confidence: 73%

“…In lung ADCs, positive immunostaining for p63 is rare; when present, it has been reported as weak and focal [5,[9][10][11][12][13]. Only in 5.5% of cases has coexpression of both TTF-1 and p63 in the same cellular elements been reported [10][11][12]14,15].…”

Section: Discussionmentioning

confidence: 99%

“…In non-neoplastic tissue, p63 is expressed in the basal reserve cells of stratified squamous epithelia and of gland epithelium [11,12]. The positivity of p63 has even been reported in the terminal bronchioles [13].…”

Section: Discussionmentioning

confidence: 99%

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TTF-1/p63-Positive Poorly Differentiated NSCLC: A Histogenetic Hypothesis from the Basal Reserve Cell of the Terminal Respiratory Unit

et al. 2020

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TTF-1 is expressed in the alveolar epithelium and in the basal cells of distal terminal bronchioles. It is considered the most sensitive and specific marker to define the adenocarcinoma arising from the terminal respiratory unit (TRU). TTF-1, CK7, CK5/6, p63 and p40 are useful for typifying the majority of non-small-cell lung cancers, with TTF and CK7 being typically expressed in adenocarcinomas and the latter three being expressed in squamous cell carcinoma. As tumors with coexpression of both TTF-1 and p63 in the same cells are rare, we describe different cases that coexpress them, suggesting a histogenetic hypothesis of their origin. We report 10 cases of poorly differentiated non-small-cell lung carcinoma (PD-NSCLC). Immunohistochemistry was performed by using TTF-1, p63, p40 (∆Np63), CK5/6 and CK7. EGFR and BRAF gene mutational analysis was performed by using real-time PCR. All the cases showed coexpression of p63 and TTF-1. Six of them showing CK7+ and CK5/6− immunostaining were diagnosed as "TTF-1+ p63+ adenocarcinoma". The other cases of PD-NSCLC, despite the positivity for CK5/6, were diagnosed as "adenocarcinoma, solid variant", in keeping with the presence of TTF-1 expression and p40 negativity. A "wild type" genotype of EGFR was evidenced in all cases. TTF1 stained positively the alveolar epithelium and the basal reserve cells of TRU, with the latter also being positive for p63. The coexpression of p63 and TTF-1 could suggest the origin from the basal reserve cells of TRU and represent the capability to differentiate towards different histogenetic lines. More aggressive clinical and morphological features could characterize these "basal-type tumors" like those in the better known "basal-like" cancer of the breast.Diagnostics 2020, 10, 25 2 of 9 characterized by predominantly solid growth, formed by cells with large, eosinophilic cytoplasm, with a misleading tendency to keratinization or a pseudosquamoid morphology. Thus, histochemical detection of mucin and immunohistochemistry are often essential tests in differential diagnosis of NSCLCs, expanding the routine morphological examination.The combined use of antibodies TTF-1 and cytokeratin 7 (CK7) for ADC and p63 with high molecular weight keratins (CK5/6) for SCC provides a very reliable distinction between these two subtypes of non-small-cell carcinoma [1,2]. Recently, p40 has been considered the most specific marker of SCC [3]. SCC shows positive immunostaining for CK5/6, p63 and p40 (∆Np63) (with strong and widespread nuclear reaction) and negative immunostaining for TTF-1 and CK7. In contrast, ADC shows positive immunostaining for TTF-1 and CK7 and negative immunostaining for p63, p40 and CK5/6 [3,4]. Even if few ADCs may stain positively for p63, they show only a focal and weak positivity [5], while CK5/6 and p40 expression is usually absent. CK5/6-positive immunostaining is very unusual in ADCs, and even if it is present, in the absence of p63 and p40, it is not sufficient to support the squamous differentiation [3][4][5][6]. For SCC, p63 and CK...

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Section: Discussionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 99%

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TTF-1/p63-Positive Poorly Differentiated NSCLC: A Histogenetic Hypothesis from the Basal Reserve Cell of the Terminal Respiratory Unit

et al. 2020

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“…To find differentially expressed genes between lung cancer subtypes, we used only tumor samples of different subtypes as sample groups. Because of the small sample size and similar histology27 of AC and BC samples we used these in analyses as one group. We identified 112 genes which were up-regulated and 101 genes which were down-regulated in AC/BC compared to the SCC (Supplemental Fig.…”

Section: Resultsmentioning

confidence: 99%

Metagenes Associated with Survival in Non-Small Cell Lung Cancer

et al. 2011

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NSCLC (non-small cell lung cancer) comprises about 80% of all lung cancer cases worldwide. Surgery is most effective treatment for patients with early-stage disease. However, 30%–55% of these patients develop recurrence within 5 years. Therefore, markers that can be used to accurately classify early-stage NSCLC patients into different prognostic groups may be helpful in selecting patients who should receive specific therapies.A previously published dataset was used to evaluate gene expression profiles of different NSCLC subtypes. A moderated two-sample t-test was used to identify differentially expressed genes between all tumor samples and cancer-free control tissue, between SCC samples and AC/BC samples and between stage I tumor samples and all other tumor samples. Gene expression microarray measurements were validated using qRT-PCR.Bayesian regression analysis and Kaplan-Meier survival analysis were performed to determine metagenes associated with survival. We identified 599 genes which were down-regulated and 402 genes which were up-regulated in NSCLC compared to the normal lung tissue and 112 genes which were up-regulated and 101 genes which were down-regulated in AC/BC compared to the SCC. Further, for stage Ib patients the metagenes potentially associated with survival were identified.Genes that expressed differently between normal lung tissue and cancer showed enrichment in gene ontology terms which were associated with mitosis and proliferation. Bayesian regression and Kaplan-Meier analysis showed that gene-expression patterns and metagene profiles can be applied to predict the probability of different survival outcomes in NSCLC patients.

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“…XIAP, cIAP1 and cIAP2 are expressed in normal tissue, but numerous studies have indicated upregulation of these proteins in cancer cell lines and tissues [38][39][40][41][42][43][44][45][46][47][48][49][50][51]. Although some studies have found a correlation between these IAPs expression levels and chemoresistance, poor prognosis or cancer progression [38,41,[52][53][54][55][56][57][58][59][60], others have not [61][62][63].…”

Section: The Role Of Iaps In Cancermentioning

confidence: 98%

Targeting IAPs as An Approach to Anti-Cancer Therapy

Straub¹

2011

CTMC

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Apoptosis is an essential process for embryonic and lymphocyte development, immune system modulation and tissue homeostasis. Defects in apoptotic signaling often lead to diseases of immune deficiency, neurodegeneration and cancer [1, 2]. In the cancer arena, these defects may contribute to the establishment and growth of tumors. Moreover, many cytotoxic chemotherapies act in part by activating these apoptotic networks. Occasionally apoptotic pathways are activated, however key players downstream of initiation are inhibited by negative regulators that have been dysregulated by the diseased state of the cell. Removal of these barriers to apoptosis signaling, it has been rationalized, could restore cell death in diseased cells while sparing those that are not primed for programmed cell death. Additionally, the subversion of these death evading mechanisms may re-sensitize cells that have developed resistance to chemotherapies in this manner. The importance of apoptosis as a maintenance process, and the promise that restoring this signaling could mean in treating cancer has placed many targets on the front line of oncology research. Approaches are being developed that will activate death receptor pathways, synthetically activate caspases, restore the activity of tumor suppressor genes such as p53, and counteract the effects of anti-apoptotic factors. Among these approaches, small molecules are in clinical trials against several anti-apoptotic players, namely the Bcl-2 and IAP proteins. This review will focus on the efforts being advanced against the Inhibitor of Apoptosis Proteins (IAP), the chemical matter of the inhibitors and the biology emerging from this research.

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Immunohistochemical detection of XIAP and p63 in adenomatous hyperplasia, atypical adenomatous hyperplasia, bronchioloalveolar carcinoma and well-differentiated adenocarcinoma

Cited by 24 publications

References 30 publications

TTF-1/p63-Positive Poorly Differentiated NSCLC: A Histogenetic Hypothesis from the Basal Reserve Cell of the Terminal Respiratory Unit

TTF-1/p63-Positive Poorly Differentiated NSCLC: A Histogenetic Hypothesis from the Basal Reserve Cell of the Terminal Respiratory Unit

Metagenes Associated with Survival in Non-Small Cell Lung Cancer

Targeting IAPs as An Approach to Anti-Cancer Therapy

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