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Wei-Chin Chang
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MA09 - Lung Cancer Surgical and Molecular Pathology (ID 908)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Pathology
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 15:15 - 16:45, Room 202 BD
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MA09.07 - Developing a Pathological Grading System in Predicting Prognosis for Invasive Mucinous Adenocarcinomas (ID 12124)
15:55 - 16:00 | Presenting Author(s): Wei-Chin Chang
- Abstract
- Presentation
Background
Invasive mucinous adenocarcinoma (IMA) is a variant of lung adenocarcinoma with a predominance of mucinous type neoplastic epithelial cells, often showing aerogenous spreading and multifocality. The correlation between histopathological features and prognosis has not been well studied due to its relatively rare incidence compared to non-mucinous adenocarcinoma. Our study aims to evaluate the significance of histopathological features in relation to clinical outcome.
a9ded1e5ce5d75814730bb4caaf49419 Method
We reviewed a series of 101 cases of IMAs resected between 2000 to 2012, comprised of stage I~IV tumours. Five pathological features were scored for each tumour: predominant histological pattern (lepidic: 1, acinar/papillary: 2, solid/micropapillary/cribriform: 3), nuclear atypia (mild:1, moderate: 2, severe: 3), mitotic activity per 2mm2 (<4: 0, ≥4: 1), necrosis (absent: 0, present: 1), lymphovascular invasion (absent: 0, present: 1), and pleural invasion (PL0: 0, PL1: 1, PL2: 2, PL3: 3). Each pathological feature was correlated with disease-free (DFS) and overall survival (OS). Cases were then divided into three grades based on the total pathological score (grade I: 2-4, grade II: 5-7, grade III: 8-11) and correlated with outcome.
4c3880bb027f159e801041b1021e88e8 Result
Nuclear atypia, mitotic activity, lymphovascular invasion, and pleural invasion showed significant correlation with OS (p < 0.05). Histological pattern and necrosis showed no significant correlation in relation to OS (p = 0.09). Pleural invasion and lymphovascular invasion were significantly correlated with DFS (p < 0.05), while a trend was noted for nuclear atypia (p = 0.086). No correlation with DFS was seen for histological pattern (p = 0.499), necrosis (p = 0.464), and mitotic activity (p = 0.931). There was an inverse correlation between OS and grade, with grade III tumours showing a significantly worse prognosis (p = 0.001). There was no significant difference in DFS between the three groups (p = 0.201).
8eea62084ca7e541d918e823422bd82e Conclusion
Our pathological scoring system was able to stratify IMAs into three separate groups with statistically significant differences in overall survival between grade III and grades I/II tumours.
6f8b794f3246b0c1e1780bb4d4d5dc53Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MA21 - Molecular Subtyping, CBL3, and Non Coding RNA (ID 924)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Biology
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 15:15 - 16:45, Room 205 BD
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MA21.03 - Heterogeneity in MET Copy Number and Intratumoural Subsets in Pleomorphic Lung Carcinoma: Implications for MET Directed Therapy in NSCLC (ID 13061)
15:25 - 15:30 | Author(s): Wei-Chin Chang
- Abstract
- Presentation
Background
Pleomorphic Lung Carcinoma (PC) is a rare subtype of NSCLC poorly responsive to systemic therapy. Both epithelial and sarcomatoid phenotypes exist, suggesting an important role of epithelial-to-mesenchymal transition. We aimed to determine MET copy number (CN) within individual tumour components and establish its correlation with immunohistochemistry (IHC) expression.
a9ded1e5ce5d75814730bb4caaf49419 Method
Histopathological assessment and diagnosis was confirmed for 57 cases of resected PCs from the Royal Brompton Hospital Biobank. DNA was isolated from multiple regions and MET copy number determined by digital droplet PCR (ddPCR). IHC using c-MET (EP1454Y) and H-scores were assigned independently by two histopathologists.
4c3880bb027f159e801041b1021e88e8 Result
Cases: median age 66 years, 36.2% T3, 41.4% T2 and 13.8% T1. In the epithelial areas, adenocarcinoma was the most common (45.6%) followed by undifferentiated NSCLC (22.8%) and squamous (17.5%): in pleomorphic areas, mixed giant/spindle cell (35%), spindle cell (31%) and giant cell (26%). MET-CN gain by ddPCR was seen in 25/58 (44%) of cases (CN>2.3). 3/58 (5%) had CN>5. There was a significantly higher MET-CN in pleomorphic compared to epithelial areas (2.7 versus 2.2 P = 0.046). While this did not correlate with c-MET IHC, an H-score of >223 had 75% sensitivity and 52.4% specificity for MET-CN >5.0 (Figure).
8eea62084ca7e541d918e823422bd82e Conclusion
There is intra-tumoral heterogeneity in MET-CN between tumoural subsets. This may account for the development of pleomorphic phenotypes in PC. Consequently MET-directed therapies such as crizotinib may be highly effective only against the MET-amplified component in PC and may not impact on overall tumoural control due to minimal efficacy in the non-amplified epithelial component. MET expression using IHC does not correlate with MET-CN determined by ddPCR, although may provide a screening tool for MET amplification. MET aberrations are potentially druggable and therefore this has implications for sampling and MET testing.
6f8b794f3246b0c1e1780bb4d4d5dc53Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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P1.09 - Pathology (Not CME Accredited Session) (ID 941)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.09-25 - Invasive Size (Not Total Size) Predicts Overall Survival in Invasive Mucinous Adenocarcinomas (ID 12127)
16:45 - 18:00 | Presenting Author(s): Wei-Chin Chang
- Abstract
Background
The 8th TNM pathological staging system advocates usage of the invasive size, rather than the total size, in the pT staging of pulmonary non-mucinous adenocarcinomas. However, few studies have addressed this issue regarding invasive mucinous adenocarcinomas (IMAs). Our study aimed to determine whether invasive size correlates with individual histological parameters and also whether it provides better prognostic stratification than overall tumour size.
a9ded1e5ce5d75814730bb4caaf49419 Method
We reviewed a series of 101 cases of IMAs resected between 2000 to 2012, comprised of stage I~IV tumours. In each IMA, the percentage of each growth pattern (lepidic, acinar, papillary, solid, micropapillary, and cribriform) was assessed in 5% increments. Due to the frequent multifocal nature of IMAs, the invasive size was calculated by multiplying the total tumour size with the total percentage of invasive (non-lepidic) components in all cases. The adjusted T (aT) stage, as determined by the cumulative size of invasive components, was correlated with disease-free (DFS) and overall survival (OS). Correlation with 7th and 8th T stage (using total tumour size) were also performed as comparison.
4c3880bb027f159e801041b1021e88e8 Result
The 7th aT stage was positively correlated with higher host response (tumour-associated inflammation), necrosis, pleural invasion, and nodal metastasis, while the 8th aT stage was significantly correlated with necrosis, vascular invasion, pleural invasion, and nodal metastasis. Using aT stage for risk stratification, we found a significant difference in OS in both 7th and 8th aT stage between the subgroups (p = 0.002 and 0.006, respectively), whereas DFS failed to reach statistical significance. There was a significant difference in DFS when using the 8th T stage (p = 0.002), whereas no significant difference was noted in OS. A trend was noted in DFS (p = 0.054) while OS failed to reach statistical significance when applying the 7th T staging.
8eea62084ca7e541d918e823422bd82e Conclusion
Our study showed that invasive size may be a superior prognostic indicator compared to total size, which provides a rationale for prognostic stratification of IMAs based on the extent of invasive growth patterns (or invasive size) rather than total tumour size.
6f8b794f3246b0c1e1780bb4d4d5dc53
