Distinct genetic aberrations in oesophageal adeno and squamous carcinoma

Pandilla, Ramaswamy; Kotapalli, Viswakalyan; Gowrishankar, Swarnalata; Chigurupati, MohanaVamsy; Patnaik, Sujit Chyau; Uppin, Shantveer G; Rao, Subramanyeshwar; Kalidindi, NarasimhaRaju; Sastry, R A; Challa, Sundaram; Srinivasulu, Mukta; Vasala, Anjayneyulu; Bashyam, Murali D.

doi:10.1111/eci.12163

Cited by 24 publications

(31 citation statements)

References 24 publications

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“…IHC was performed as per standard protocols [7] on tissues embedded into FFPE blocks mentioned above, as per standard practice though we are aware that this slice of tissue may not represent the whole tumor. 4 μM tumor sections were deparafinized and rehydrated in graded series of alcohol followed by heat induced epitope retrieval in citrate buffer at pH 6.0 (for p53) or proteinase K pretreatment (for epidermal growth factor receptor (EGFR)) and subjected to peroxidase quenching using 0.6% hydrogen peroxide in methanol.…”

Section: Methodsmentioning

confidence: 99%

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P53 nuclear stabilization is associated with FHIT loss and younger age of onset in squamous cell carcinoma of oral tongue

et al. 2014

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BackgroundSquamous cell carcinoma of tongue (SCCT) is expected to harbor unique clinico-pathological and molecular genetic features since a significant proportion of patients are young and exhibit no association with tobacco or alcohol.MethodsWe determined P53, epidermal growth factor receptor, microsatellite instability, human papilloma virus infection and loss of heterozygosity status at several tumor suppressor loci in one hundred and twenty one oral SCCT (SSCOT) samples and analyzed their association with clinico-pathological features and patient survival.ResultsOur results revealed a significantly higher incidence of p53 nuclear stabilization in early (as against late) onset SCCOT. FHIT loss was significantly associated with p53 nuclear stabilization and the association was stronger in patients with no history of tobacco use. Samples harboring mutation in p53 DNA binding domain or exhibiting p53 nuclear stabilization, were significantly associated with poor survival.ConclusionOur study has therefore identified distinct features in SCCOT tumorigenesis with respect to age and tobacco exposure and revealed possible prognostic utility of p53.

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Section: Methodsmentioning

confidence: 99%

“…Suspected in-dels were confirmed using TA cloning vector (Invitrogen, Carlsbad, CA, USA) as per standard procedure. PCR based screening of HPV was carried out as per standard protocol [7] with GP5 + and GP6 + primers using DNA isolated from frozen tumor tissue as template. Primer sequences are given in supplementary Additional file 2: Table S2.…”

Section: Methodsmentioning

confidence: 99%

P53 nuclear stabilization is associated with FHIT loss and younger age of onset in squamous cell carcinoma of oral tongue

et al. 2014

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“…In colorectal adenocarcinoma, the Bethesda panel mentioned above, was developed for detecting hereditary non-polyposis colorectal cancer at National Cancer Institute-sponsored MSI workshop in 1997 [10]. To our best knowledge, there are 16 studies that investigated the MSI status, focusing on EGJ adenocarcinoma (Table 1) [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]. All those studies used genetic testing.…”

Section: Previous Studies Examining Msi Status In Egj Adenocarcinomamentioning

confidence: 99%

Recent Incidence Trend of Surgically Resected Esophagogastric Junction Adenocarcinoma and Microsatellite Instability Status in Japanese Patients

et al. 2018

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Background: The incidence trend of esophagogastric junction (EGJ) adenocarcinoma in Japan has not been sufficiently investigated. Little is known about the microsatellite instability (MSI) status of this tumor. Summary: Previously published studies analyzing the trend of EGJ adenocarcinoma in Japan were reviewed. And a trend of surgically resected cases (Siewert type I-III) utilizing a retrospective multicenter cohort of 379 patients from 4 academic institutions in Japan investigated. Although an increasing trend in the last 2 reports was considered controversial, our cohort demonstrated a growing number of EGJ adenocarcinoma cases between 2006 and 2013. This trend was evident, especially in Siewert type I cases. In the previous 16 studies that performed MSI testing, MSI-high tumors ranged 0–8.3%, though there were no fixed microsatellite markers on EGJ adenocarcinoma. In a recent comprehensive genetic analysis by The Cancer Genome Atlas, MSI testing using the following 7 markers, BAT25, BAT26, BAT40, D2S123, D5S346, D17S250 and TGFR-II showed a favorable correlation with hypermutated tumors. We performed MSI testing using 6 of those markers, except TGFR-II, on 206 cases from one institution, and detected 15 cases (7.3%) with MSI-high. The prevalence of MSI-high was 0% in Siewert type I, 7.6% in type II, and 16.7% in type III. Key message: The number of surgically resected EGJ adenocarcinoma cases gradually increased, and MSI-high was infrequent in Siewert type I-II tumors in our Japanese cohort. Considering MSI-high as a predictive biomarker for emerging immune checkpoint inhibitors, MSI status is becoming more beneficial in EGJ adenocarcinoma.

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“…An evaluation of whole-tumor sections from a subset of 45 tumors revealed that the frequency of PD-L1 positive immune cells was somewhat higher [35.6% (16/45) of cases, of which 7/16 were not identified on the TMA], although still lower than that reported in GC. Interestingly, Barrett'sassociated EAC has been reported to have a low frequency of MSI and EBV (see below) (37,38).…”

Section: Pd-l1 Expression In Gastro-esophageal Tumorsmentioning

confidence: 99%

“…MSI was detected in 6.6% (5/76) of patients with Barrett'sassociated EAC, with the presence of MSI limited to AC cells, and not in adjacent Barrett's or normal epithelia (37,38). MSI has been less well studied in ESCC, although it has been detected in a subset of patients (110)(111)(112).…”

Section: Mismatch Repair (Mmr) Deficiency and Hypermutation In Gastromentioning

confidence: 99%

The promise of PD-1 inhibitors in gastro-esophageal cancers: microsatellite instability vs. PD-L1

Jin

Yoon

2016

J. Gastrointest. Oncol.

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Preliminary clinical studies of anti-programmed cell death-1 (anti-PD-1) therapy in gastroesophageal cancers have suggested promising single-agent activity. In patients who received prior treatment for advanced disease, pembrolizumab has been associated with a response rate of 20% in programmed cell death-1 ligand 1 (PD-L1)-positive tumors, and nivolumab with a response rate of 12% in unselected tumors.Both agents yielded a median duration of response lasting ~6-7 months. PD-L1 expression and microsatellite instability (MSI) have emerged as potential predictive markers for PD-1/PD-L1 blockade. PD-L1 expression in tumor cells and in immune cells within the tumor microenvironment has been detected in 14-24% and ~35% of patients with gastro-esophageal cancer, respectively. PD-L1 tumor cell expression appears to be more common in Epstein-Barr virus (EBV)-positive gastric cancers (GCs) and has been associated with an increased density of tumor-infiltrating lymphocytes (TIL). To date, data are too sparse to determine whether PD-L1 expression predicts efficacy of anti-PD-1 therapy in gastro-esophageal cancer, but data from other tumor types have not been consistent regarding its predictive value. MSI occurs in 10-20% of gastro-esophageal cancers and arises from deficient mismatch repair (MMR). MSI is highly correlated with non-synonymous mutation burden, as well as a dense accumulation of TILs. MSI has been associated with improved response to anti-PD-1 therapy in gastrointestinal cancers. Multiple studies are ongoing which examine therapeutic blockade of the PD-1/PD-L1 axis in unselected patients with gastro-esophageal cancer, as well as patients whose tumors express PD-L1 or exhibit MSI. These studies will clarify their activity in this disease and potentially can determine whether identify a strong predictive biomarker can be identified.Checkpoint inhibition is also being studied in combination with curative-intent chemo (radio) therapy and surgery.Keywords: Programmed cell death-1 (PD-1); programmed cell death-1 ligand 1 (PD-L1); gastro-esophageal cancer; microsatellite instability (MSI)

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Distinct genetic aberrations in oesophageal adeno and squamous carcinoma

Cited by 24 publications

References 24 publications

P53 nuclear stabilization is associated with FHIT loss and younger age of onset in squamous cell carcinoma of oral tongue

P53 nuclear stabilization is associated with FHIT loss and younger age of onset in squamous cell carcinoma of oral tongue

Recent Incidence Trend of Surgically Resected Esophagogastric Junction Adenocarcinoma and Microsatellite Instability Status in Japanese Patients

The promise of PD-1 inhibitors in gastro-esophageal cancers: microsatellite instability vs. PD-L1

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