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S. Matsumoto
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OA10 - EGFR Mutations (ID 382)
- Event: WCLC 2016
- Type: Oral Session
- Track: Biology/Pathology
- Presentations: 1
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OA10.02 - Association of Variations in HLA-Class II and Other Loci with Susceptibility to EGFR-Mutated Lung Adenocarcinoma (ID 4192)
11:00 - 12:30 | Author(s): S. Matsumoto
- Abstract
- Presentation
Background:
Lung adenocarcinoma (LADC) driven by somatic EGFR mutations is more prevalent in East Asians (30-50%) than in European/Americans (10-20%). Understanding the genetic factors underlying such LADC is required to elucidate disease etiology and to identify effective methods of prevention.
Methods:
We investigate genetic factors underlying the risk of this disease by conducting a genome-wide association study, followed by two validation studies, in 3,173 Japanese patients with EGFR mutation-positive lung adenocarcinoma and 15,158 controls.
Results:
Four loci, 5p15.33 (TERT), 6p21.3 (BTNL2, HLA-class II), 3q28 (TP63) and 17q24.2 (BPTF), previously shown to be strongly associated with overall lung adenocarcinoma risk in East Asians, were re-discovered as loci associated with a higher susceptibility to EGFR mutation-positive lung adenocarcinoma. In addition, two additional loci, HLA-class II at 6p21.32 and 6p21.1 (FOXP4) were newly identified as loci associated with EGFR mutation-positive lung adenocarcinoma (Shiraishi et al., Nature Communications, 2016, in press).
Conclusion:
This study indicates that multiple genetic factors, including an immunologic one, underlie the risk of lung adenocarcinomas with EGFR mutations.
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P3.01 - Poster Session with Presenters Present (ID 469)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 2
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.01-016 - Factors Influencing the Concordance of Histological Subtype Diagnosis by Biopsy and Resected Specimens of Lung Adenocarcinoma (ID 5018)
14:30 - 15:45 | Author(s): S. Matsumoto
- Abstract
Background:
Lung adenocarcinoma is heterogeneous, characterized by various histological subtypes. Determination of the predominant histological subtype (lepidic, papillary, acinar or solid-predominant) has been shown to correlate with genetic abnormalities and clinicopathological features. Although subtyping using small biopsy samples is important for tailored approaches to clinical management, limited data exist on the concordance of predominant subtype between resected specimens and biopsy specimens.
Methods:
We compared the diagnosed predominant subtypes in resected specimens and matched biopsy specimens in a series of 327 lung adenocarcinomas. Histological subtyping of preoperative material was made by review of archived hematoxylin and eosin stain slides that had originally been prepared for diagnosis before surgery. The histological subtype of surgically resected tumors was obtained from the pathological case records for each surgical resection specimen. The accuracy of preoperative diagnosis by biopsy and the factors that influence concordance with resected specimen analysis were examined.
Results:
In 211 of the 326 patients (66.0%), the predominant adenocarcinoma subtype diagnosed from biopsy matched the findings of resection analysis. Concordance rate was highest in papillary pattern (82%), followed by lepidic pattern (75%), solid pattern (66%), and acinar pattern (39%). Overall, the concordance rate in biopsy samples with larger tumor areas (≥0.7 mm[2]) was significantly higher than in those with smaller tumor area (<0.7 mm[2]; 71% vs 58%, respectively; p = 0.02). Other factors in biopsy samples, such as number of biopsies, or the small biopsy type, did not have significant influence on the concordance between preoperative and postoperative diagnosis. In the biopsy samples with smaller tumor areas, the concordance rate was 77% in lepidic subtype, 71% in papillary subtype, 60% in solid subtype, and 40% in acinar subtype. Concordance rate in the biopsy samples with larger tumor area was higher in papillary and solid subtypes (88% and 76%, respectively), but remained low in acinar subtype (37%).
Conclusion:
These results indicate that accuracy of adenocarcinoma subtyping based on small biopsy samples is influenced by tumor area. Our study also suggests that subtyping of acinar histology using biopsy specimen is particularly error-prone.
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P3.01-033 - Changes in the Tumor Microenvironment during Lymphatic Metastasis of Lung Squamous Cell Carcinoma (ID 6341)
14:30 - 15:45 | Author(s): S. Matsumoto
- Abstract
Background:
Metastasis and growth in neoplastic lesions requires the multi-step regulation of microenvironmental factors. We aimed to elucidate the microenvironmental changes in the process of lymphatic metastasis of lung squamous cell carcinoma.
Methods:
We examined the morphological characteristics of 102 cases of Primary Tumor (PT), 50 of intralymphatic tumor (ILT), 51 of lymph node (LN) micrometastasis (LN-Mic; less than 2 mm in size) and 82 of LN Macrometastasis (LN-Mac; greater than 10 mm in size). Afterwards we evaluated the expression of nine molecules (EGFR, FGFR2, CD44, ALDH1, Podoplanin, E-cadherin, S100A4, geminin and ezrin) in matched PT, ILT, LN-Mic and LN-Mac from 23 of these cases.
Results:
The number of smooth muscle actin α-positive fibroblasts, CD34-positive microvessels and CD204-positive macrophages were also examined. As a result, the mitotic index of cancer cells was significantly lower in ILT and LN-Mic than PT and LN-Mac (p<0.001). Moreover stromal reaction in ILT and LN-Mic was less prominent than in PT and LN-Mac (p<0.001). Immunohistochemical study revealed that EGFR expression level and frequency of geminin positive cells in ILT and LN-Mic were significantly lower than in PT and LN-Mac (p<0.05). The number of stromal cells indicated by staining of CD34, CD204 and smooth muscle actin α in ILT and LN-Mic also was significantly lower than in PT and LN-Mac (p<0.05).
Conclusion:
In lung squamous cell carcinoma, drastic microenvironmental changes (e.g., growth factor receptor expression and proliferative capacity of cancer cells and structural changes in stromal cells) occur during both the process of lymphatic permeation and the progression into macrometastases.
