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T. Kondo



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    P2.18 - Poster Session 2 - Pathology (ID 176)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Pathology
    • Presentations: 2
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      P2.18-019 - Clinicopathological features in non-small cell lung cancer patients with EGFR and KRAS mutations. (ID 2985)

      09:30 - 09:30  |  Author(s): T. Kondo

      • Abstract

      Background
      Some of molecular pathways have been shown to have prognostic impact in non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) mutations predict the effect of EGFR tyrosine kinase inhibitors. KRAS is also critical oncogene, and it has been reported that KRAS pathway might interact with EGFR. But, the role of KRAS in NSCLC is unclear. We investigated the relationship between EGFR and KRAS mutation status and clinicopathological features in NSCLC.

      Methods
      A total of 383 consecutive patients with NSCLC underwent complete resection from 2006 to 2008 were examined retrospectively. The expression of EGFR and KRAS were evaluated by tissue microarray.

      Results
      The mutations of EGFR and KRAS were detected in 181/383 (47.3%) and 32/383 (8.4%) patients, respectively. On analysis of EGFR mutations, female were 107/181 (59.1%) and 51/202 (25.2%), adenocarcinoma were 177/181 (97.8%) and 123/202 (60.9%), no vascular invasion were 147/181 (81.2%) and 110/202 (54.5%), and non-smoker were 99/181 (54.7%) and 41/202 (20.3%) patients in EGFR mutation and wild type patients, respectively. As a result, EGFR mutation was found more frequently in female, adenocarcinoma, no vascular invasion, and non-smoker. The number of patients with pathological T1a were 49/181 (27.0%) and 42/202 (20.8%), T1b were 63/181 (34.8%) and 41/202 (20.3%) in EGFR mutation and wild type patients, respectively. Moreover, average tumor diameter was smaller in patients with EGFR mutation (2.68 cm±0.92) than wild type (3.34cm±1.70) (P<0.001). There were no differences in clinicopathological characteristics between exon19 and 21 EGFR mutations. In contrast, there were no significant differences between KRAS mutation and gender, histopathological type, vascular invasion and.smoking. Although KRAS status was not correlated with pathological T factors, average tumor diameter was larger in patients with KRAS mutation (3.49 cm±2.00) than wild type (2.98 cm±1.35) (P<0.001).

      Conclusion
      Our results suggest that EGFR mutation may suppress vascular invasion, and tumor growth, on the other hand, KRAS mutation may correlate with activation of tumor growth.

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      P2.18-020 - Appropriateness Evaluation of Handling Method for the Small Lung Adenocarcinoma in the Frozen Section Diagnosis by Radiological-Pathological Correlation (ID 3007)

      09:30 - 09:30  |  Author(s): T. Kondo

      • Abstract

      Background
      The frozen section diagnosis is often performed in the sublobar resection of lung tumor. As no standard of preparation method for the frozen section is proposed, its methodology differs depending on institutions. In this study, we examine appropriateness of our preparation method for a resected specimen with a small adenocarcinoma by comparing between radiological and pathological tumor size.

      Methods
      We retrospectively reviewed the records of 59 resected lung specimens for the frozen section diagnoses (54 wedges and 5 segmentectomies) of lung adenocarcninomas from January to December 2008. After the specimen was well inflated with saline using injector, the pathologist cut it into segments with a width of 3-5mm and immersed them in saline. Taking the segment with maximum diameter of tumor as a sample, the pathological tumor sizes were measured (I) macroscopically by using metal straight ruler, (II) microscopically on the frozen section, and (III) microscopically on the permanent paraffin section. For obtaining the stereoscopic tumor size (Ⅱ and Ⅲ), we used a stereoscopic image analysis software, Leica Application Suite (Leica Microsystems; Tokyo, Japan). CT tumor size was measured by using 1-2mm thin-section CT (X-Vigor/Real or Aquillion, Toshiba Medical Systems, Tokyo, Japan). We obtained the tumor shadow disappearance rate (TDR) by comparing tumor size on the lung and mediastinal window image, to classify 59 cases into two groups according to TDR; TDR≧50% defined as the air-containing type (Group A, n=44) and TDR＜50% as the solid-containing type (Group S, n=15). We also calculated the diremption rate (DR%) between the pathological and the CT tumor size (DR% = |CT tumor size － each pathological tumor size|/CT tumor size×100(%)) and compared Group A and Group S.

      Results
      Mean CT tumor size and its standard deviation(SD) were 18.36±5.23mm, and mean pathological tumor sizes and SD of Ⅰ, Ⅱ, and Ⅲ were 17.17±6.12, 14.29±3.66, and 14.23±4.38mm, respectively. Mean CT tumor size was statistically larger than that of Ⅱ and Ⅲ (p<0.001 using Paired t-test). All the three pathological tumor sizes were correlated to the CT tumor size by Pearson’s correlation analysis (correlation coefficient were 0.766, 0.700, and 0.682, respectively). DR% of Ⅱ and Ⅲ were significantly higher in Group A than Group S by Mann-Whitney U-test (Mean DR% of group A / S (p-values) of Ⅰ, Ⅱ, and Ⅲ were 17.0/13.8% (p=0.196), 25.8/19.3% (p=0.093), and 27.3/15.5% (p=0.032) , respectively).

      Conclusion
      There was a strong correlation between CT tumor size and each pathological tumor size, which shows that our preparation method of the specimen for the frozen section is appropriate to obtain sufficient information about the lung tumor. Furthermore, we found that the pathological tumor size is considerably underestimated by measuring tumor size on the frozen or permanent paraffin section, especially the tumor classified as “air-containing type” including adenocarcinoma with good prognosis. It is therefore important to inflate the lung specimen sufficiently and to transfer it to microscopical examination without tissue shrinking.

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    P3.19 - Poster Session 3 - Imaging (ID 181)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Imaging, Staging & Screening
    • Presentations: 2
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      P3.19-003 - The correlation between computed tomography findings and the clinicopathological factors in small-sized adenocarcinomas of the lung (10 mm or less in diameter) (ID 1220)

      09:30 - 09:30  |  Author(s): T. Kondo

      • Abstract

      Background
      We previously reported the correlation among the thin-section computed tomography (TS-CT) findings, the pathological factors (Noguchi’s classification) and the prognosis of the patients. The purpose of this study was to examine the tumor shadow disappearance rate (TDR) on TS-CT findings, clinical course and pathological factors of small-sized adenocarcinomas of the lung according to the 2011 IASLC/ERS Classification.

      Methods
      We retrospectively analyzed 111 peripheral non-mucinous adenocarcinomas of the lung ≤ 10 mm in diameter that were surgically resected at our institute between January 1997 and February 2013. CT scans were obtained by commercially available scanners (X-Vigor/Real or Aquilion M/16 CT scanner; Toshiba Medical Systems; Tokyo, Japan). TS images were obtained with a 1 mm section thickness, pitch of 1, section spacing of 1 mm, 512 × 512 pixel resolution and 1 second scanning time. TDR was defined as the ratio of the maximum diameter of the tumor opacity of the mediastinal window to that of the lung window on TS-CT. We also examined the relationship among the TDR, the patient backgrounds, pathological findings (i.e., lymph node metastasis, pleural invasion, vascular invasion and lymphatic invasion) and clinical course. The histologic subtypes were analyzed according to the 2011 IASLC/ATS/ERS International Multidisciplinary Classification of Lung Adenocarcinoma.

      Results
      The median age of the patients was 64 (range, 23-83) years, and 66 patients (59.5%) were female. Sixty-four patients (57.7%) were never-smokers. The average tumor size was 8.7 mm (range, 5-10 mm). Regarding the histological subtypes, 70 cases were adenocarcinoma in situ (AIS) or minimally invasive adenocarcinoma (MIA), 19 were acinar predominant (AP), 13 were papillary predominant (PP) and seven were solid predominant (SP). Two cases could not be determined. Seventy cases diagnosed AIS or MIA were all stage IA, and none of these patients relapsed. Six cases relapsed after surgery; three cases of AP, two of PP and one of a SP tumor. In a comparison of the clinical course, the pathological differentiation and the TS-CT findings, all six cases relapsed after surgery showed ≤ 40% in TDR. Four cases diagnosed with lymph node metastasis (i.e., cases diagnosed in stage IIA or higher) showed ≤ 22% in TDR. Twelve cases with pleural invasion or vascular invasion or lymphatic invasion in the pathological factors of the resected lesions showed ≤ 28% in TDR. The TDR of AIS and MIA cases were all ≥ 50%.

      Conclusion
      There are sometimes pathologically invasive lesions even in small-sized adenocarcinomas of the lung. We found that the TDR is related to the clinical course and pathological factors in small-sized adenocarcinomas of the lung (10 mm or less in diameter). The lesions with a TDR ≤ 40% in the TS-CT images may be a group of highly malignant with an increased risk of relapse. The TDR may contribute to the determination of the optimal therapeutic strategy. We need a more robust prospective study to validate the efficacy of TDR.

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      P3.19-010 - The Status of EGFR Mutations in Mixed Ground-Glass Opacity (part-solid GGO) on Thin-section CT (ID 1826)

      09:30 - 09:30  |  Author(s): T. Kondo

      • Abstract

      Background
      Thin-section CT (TS-CT) provides us with a more precise image of small pulmonary carcinomas. Thin-slice sections with thicknesses of 0.5 mm-1mm reflect, with some accuracy, the histopathological findings; mixed ground-glass opacity (part-solid GGO) is one characteristic finding of pulmonary adenocarciomas. These findings are vary in appearance, for example; some contain mainly GGO components, and some contain mainly solid portions. CT findings of mixed GGO, pathological findings and prognoses have been reported. Presently, we do not fully understand the correlation between TS-CT findings of mixed GGO and the status of EGFR mutation.

      Methods
      We retrospectively reviewed the records and TS-CT scans of 115 patients with mixed GGO tumors. All patients had undergone surgical resection between 2002 and 2008. Tumor diameters measured 20mm or less in size. All TS-CT images were acquired by Aquillion CT scanner (Toshiba Medical System). TS-CT images of tumors were obtained at 135kVp at 250mAs with 0.5-1mm section thickness. All images were photographed using mediastinal (level, 40HU; width, 400HU) and lung (level, -600HU); width, 1600HU) window settings. All TS-CT images on lung window setting were classified as: (1) Predominant GGO type (pGGO; solid portion areas less than 50% of tumor), (2) Heterogeneous type (heterogenous increased density), (3) Predominat solid type (pSolid; Solid portion areas took up more than 50% of tumor). We analyzed EGFR and Kras mutations, and then studied the correlations between these TS-CT findings and the status of EGFR mutations.

      Results
      The tumors in all 115 cases were well-differentiated adenocarcinomas. GwS type; 24 cases, Heteogenous type; 30 cases, and SwG type 61 cases. The EGFR mutation ratio was 66.6% in pGGO type, 90% in Heterogenous type and 52.7% in pSolid type. The ratio of EGFR mutation was greater in Heterogenous types compared to pGGO and pSolid types. (pGGO/Hetero p=0.045, pSolid/Hetero p=0.00038).

      Conclusion
      There is a correlation between the thin-section findings of mixed GGO and the status of EGFR mutations.