Role of molecular studies in the diagnosis of lung adenocarcinoma

Yousem, Samuel A.

doi:10.1038/modpathol.2011.156

Cited by 22 publications

(15 citation statements)

References 40 publications

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“…A total number of 60 patients out of the 860 NSCLC stage IV patients tested positive for ALK mutation, and thus in principle were eligible for Crizotinib therapy. This latter number corresponds to a percentage of 3.8% ALK-positive NSCLC in the entire cohort, thus being in a range comparable to other cohorts [ 26 ]. Out of the 60 patients who were, in principle, eligible for Crizotinib therapy, only 22 received Crizotinib therapy, whilst the remaining patients received alternative or palliative therapy.…”

Section: Resultssupporting

confidence: 60%

Cost Saving Opportunities in NSCLC Therapy by Optimized Diagnostics

Nenadic

Staber

Dreier

et al. 2017

Cancers

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With an incidence of 68 new cases per 100,000 people per year, an estimated total number of up to 350,000 new non-small-cell lung cancer (NSCLC) cases are diagnosed each year in the European Union. Up to 10% of NSCLC patients are eligible for therapy with novel ALK (anaplastic lymphoma kinase) inhibitors, as they have been diagnosed with a mutation in the gene coding for ALK. The ALK inhibitor therapy costs add up to approx. 9000 € per patient per month, with treatment durations of up to one year. Recent studies have shown that up to 10% of ALK cases are misdiagnosed by nearly 40% of pathologic investigations. The current state-of-the-art ALK diagnostic procedure comprises a Fluorescent in situ Hybridization (FISH) assay accompanied by ALK inhibitor therapy (Crizotinib). The therapy success ranges between a full therapy failure and the complete remission of the tumor (i.e., healing), but the biomedical and systemic reasons for this range remain unknown so far. It appears that the variety of different ALK mutations and variants contributes to the discrepancy in therapy results. Although the major known fusion partner for ALK in NSCLC is the Echinoderm microtubule-associated protein-like 4 (EML4), of which a minimum of 15 variants have been described, an additional 20 further ALK fusion variants with other genes are known, of which three have already been found in NSCLC. We hypothesize that the wide variety of known (and unknown) ALK mutations is associated with a variable therapy success, thus rendering current companion diagnostic procedures (FISH) and therapy (Crizotinib) only partly applicable in ALK-related NSCLC treatment. In cell culture, differing sensitivity to Crizotinib has been shown for some fusion variants, but it is as yet unknown which of them are really biologically active in cancer patients, and how the respective variants affect the response to Crizotinib treatment. Moreover, it has been demonstrated that translocated ALK genes can also be observed in healthy tissues and are not compulsorily associated with tumors. Therefore, it is important to keep in mind that even for the known variants of ALK fusion genes, the biological function is not known for all variants, and that no information is available on the homogeneity of ALK fusion variants within a single tumor. These facts, in concert with data for ALK mutation prevalence and therapy outcomes of a German cohort of NSCLC patients, support the hypothesis that, by using novel companion diagnostic tools in combination with therapy outcome predictions, massive cost savings could be possible in European Health Care systems without a loss of patient care.

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Section: Resultssupporting

confidence: 60%

Cost Saving Opportunities in NSCLC Therapy by Optimized Diagnostics

Nenadic

Staber

Dreier

et al. 2017

Cancers

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“…38 Whether previous studies 30,[39][40][41] have demonstrated that mucinous adenocarcinomas of the lung tend to be wild-type at EGFR mutational analysis, herein we observed that also the other variants of primary lung and metastatic mucin-producing adenocarcinomas do not harbor EGFR mutations. Several works have underlined the significant relationship between ALK rearrangement and signet ring cell pattern of lung adenocarcinomas, [42][43][44] …”

Section: Rossi G Et Alsupporting

confidence: 49%

Napsin-A, TTF-1, EGFR, and ALK Status Determination in Lung Primary and Metastatic Mucin-Producing Adenocarcinomas

et al. 2014

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Pulmonary mucin-producing adenocarcinomas may be indistinguishable on conventional histology from a metastasis, as TTF-1 expression often is lacking and KRAS mutations are widely present even in extra-pulmonary sites. Few data have been reported on the diagnostic role of napsin-A and EGFR and ALK gene alterations in this challenging differential diagnosis. Seventy-seven surgically resected cases, including 53 primary and 24 metastatic tumors from different sites, were evaluated for Napsin-A, TTF-1 and ALK by immunohistochemistry and for EGFR mutations by direct sequencing. Overall, napsin-A expression in primary lung mucin-producing adenocarcinomas was 36% (8% mucinous, 17% colloid, 87.5% solid, and 100% signet ring cell) and TTF-1 expression reached an overall figure of 42% (12.5% mucinous, 33% colloid, 87.5% solid, and 100% signet ring cell). Metastatic mucinous adenocarcinomas did not react with napsin-A or with TTF-1. All primary and metastatic tumors lacked EGFR mutations, while a single case of signet ring cell lung adenocarcinoma showed ALK expression and rearrangement at FISH analysis.Napsin-A has a lower sensitivity compared to TTF-1 in primary mucin-producing adenocarcinomas of the lung. However, both antibodies have an absolute specificity, being always negative in metastatic mucinous adenocarcinomas. EGFR mutations and ALK translocation or expression are exceedingly rare in mucin-producing adenocarcinomas of the lung, resulting unnecessary as diagnostic tool in this setting.

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“…Improper regulation of Sox genes have been demonstrated to be associated with cancerous development of various types of cancer [20], such as gastric cancer [41,42], brain tumors [43,44], ovarian cancer [45], adenocarcinoma [46–49], hepatocarcinoma [50], breast cancer [51–53], melanomas [54], prostate cancer [55–58], colon carcinoma [59], and the lung cancer [18,36,60–69]. The role of the Sox gene family in the cancerogenesis has been attributed to their properties involving in the regulation of cell differentiation, proliferation, and survival in multiple essential processes.…”

Section: Sox Genes and Lung Cancermentioning

confidence: 99%

The Role of Sox Genes in Lung Morphogenesis and Cancer

Zhu

Wei

et al. 2012

IJMS

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The human lung consists of multiple cell types derived from early embryonic compartments. The morphogenesis of the lung, as well as the injury repair of the adult lung, is tightly controlled by a network of signaling pathways with key transcriptional factors. Lung cancer is the third most cancer-related death in the world, which may be developed due to the failure of regulating the signaling pathways. Sox (sex-determining region Y (Sry) box-containing) family transcriptional factors have emerged as potent modulators in embryonic development, stem cells maintenance, tissue homeostasis, and cancerogenesis in multiple processes. Recent studies demonstrated that the members of the Sox gene family played important roles in the development and maintenance of lung and development of lung cancer. In this context, we summarize our current understanding of the role of Sox family transcriptional factors in the morphogenesis of lung, their oncogenic potential in lung cancer, and their potential impact in the diagnosis, prognosis, and targeted therapy of lung cancer.

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Role of molecular studies in the diagnosis of lung adenocarcinoma

Cited by 22 publications

References 40 publications

Cost Saving Opportunities in NSCLC Therapy by Optimized Diagnostics

Cost Saving Opportunities in NSCLC Therapy by Optimized Diagnostics

Napsin-A, TTF-1, EGFR, and ALK Status Determination in Lung Primary and Metastatic Mucin-Producing Adenocarcinomas

The Role of Sox Genes in Lung Morphogenesis and Cancer

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