Microsatellite Instability Is Uncommon in Lymphoepithelioma-like Carcinoma of the Lung

Abstract

Primary lymphoepithelioma-like carcinoma of the lung (LELC) shares some morphologic and clinical characteristics with malignancies associated with microsatellite instability (MSI). The aims of our study were to determine the MSI status in LELC and compare these findings with stage I non-small cell lung carcinoma (NSCLC) with marked lymphocytic host response (MLHR). We assessed MSI by a DNA-based polymerase chain reaction assay using mononucleotide (BAT25 and BAT26) and dinucleotide (D2S123, D5S346, and D17S250) repeats. MSI was detected in 2 (29%) of 7 LELC cases with only 1 marker (D17S250), and in 3 (19%) of 16 NSCLC cases with MLHR with only 2 markers (1D2S123 and 2 D17S250). Loss of heterozygosity (LOH) was detected at 1 or 2 of 3 dinucleotide repeats in 11 NSCLC cases (69%) with MLHR and 3 LELC cases (43%) (P = .36). The overall frequencies of LOH in NSCLC with MLHR were 29% and 19% in LELC (P = .55). MSI is very uncommon in LELC, indicating that MSI is not an important event in carcinogenesis for this tumor subtype. The presence of LOH suggests a probable role of tumor suppressor genes in LELC carcinogenesis.

Gastrointestinal cancers accompanied by a dense lymphoid component: an overview with special reference to gastric and colonic medullary and lymphoepithelioma-like carcinomas

“…Furthermore, because of the lymphoepithelioma-like morphology, EBV infection was sought and found to be negative 36. This does appear to be a unique case and others have not found significant levels of MSI in lymphoepithelioma-like carcinomas of the lung, for instance 40. There are cases of colonic lymphoepithelioma-like carcinomas of the colon that are not arranged in syncytial sheets but rather as single cells, small clusters of tumour and occasional glands that have a predominant intra-tumoural lymphoid component.…”

Unique p53 and epidermal growth factor receptor gene mutation status in 46 pulmonary lymphoepithelioma‐like carcinomas

“…In the past two decades, there have been just over 150 cases reported in published work. (12,21,22) In our study, 16 patients were male and 30 patients were female. The male:female ratio was different from other published reports of 2.2:1 (23) and 6:5 (16) ; the male:female ratio of NSCLC was 2.2:1 in our previous study.…”

“…(24,27) The low frequency of association with cigarette smoking in LELC of the lung (13% in the current series and 40% in cases in published reports), (22,28) in contrast to other lung cancers (smoking history usually more than 60%), (29) suggests that smoking probably does not play an etiologic role, further mandating separation of this tumor from other lung cancers. (21,22) Considerable evidence indicates that the EGFR pathway also plays an important role in both the pathogenesis and the progression of lung cancer. (30) A detailed study of mutation patterns within the EGFR gene and their associations with clinicopathologic features of lung cancers suggested that lung cancer patients whose tumors have EGFR mutations respond better than those without such mutations to drugs that target the EGFR tyrosine kinase domain.…”

“…An estimated 1000 microdissected tumor cells were digested in 50 lL buffer consisting of 20 mmol ⁄ L Tris-HCl (pH 8.0), 1 mmol ⁄ L EDTA (pH 8.0), 1% Tween 20, and 1 mg ⁄ mL proteinase K for 24 h at 56°C. The protease-treated DNA mixture was heat inactivated after incubation for 10 min at 95°C, as described by Sugio et al (20) p53 exons 5, 6, 7, 8 and EGFR tyrosine kinase exons 18,19,20,21 were amplified by nested PCR, using specific primers. The primers and amplification conditions have been described previously.…”

Clinicopathologic and Molecular Profiles of Microsatellite Unstable Barrett Esophagus-associated Adenocarcinoma

“…In our cohort, we used the term "medullary" to refer to a poorly differentiated carcinoma with syncytial islands or complex collections of malignant cells exhibiting prominent infiltration by intraepithelial lymphocytes. It is noted that one can diagnose a "lymphoepithelioma-like" carcinoma when someone confronts an EBV+ medullary carcinoma, particularly in other parts of the body, 10,16,44 and we recognize that our definition of medullary carcinoma overlaps somewhat with "lymphoepithelioma-like" carcinoma in this sense. Using a similar definition, MSI-H status has been reported in 90% to 100% of medullary carcinomas of the colon, 1,21,32 which comprise only 4% of colorectal cancers.…”