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Qian Cui
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P2.09 - Pathology (ID 174)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Pathology
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.09-35 - Proposal to Revise VENTANA ALK Scoring Interpretation Guide for Non-Small Cell Lung Carcinoma: Interpretation of ALK Heterogeneity (Now Available) (ID 831)
10:15 - 18:15 | Author(s): Qian Cui
- Abstract
Background
A small number of non-small cell lung cancer (NSCLC) cases showed heterogeneity of anaplastic lymphoma kinase (ALK) by VENTANA immunohistochemistry (IHC) in clinical practice. According to the ALK Scoring Interpretation Guide for VENTANA anti-ALK (D5F3), the presence of strong granular cytoplasmic staining in tumor cells (any percentage of positive tumor cells) is called positive for ALK. However, we know little about ALK heterogeneous cases. Multiple detection platforms are used to analyze molecular variability and pathological features in anticipation of clinical treatment decisions for such cases.
Method
A total of 2228 NSCLC cases with successful ALK IHC (VENTANA, D5F3, Roche) detection in Guangdong Provincial People`s Hospital were recruited between January 2012 and April 2018. Positive and negative system control and a negative agent control were established for each case. ALK IHC positivity was defined as the presence of strong granular cytoplasmic staining in 100% tumor cells; ALK IHC heterogeneity as the presence of strong granular cytoplasmic staining in 1-99% tumor cells; ALK IHC negativity as no tumor cells show strong granular cytoplasmic staining. Fluorescence in-situ hybridization (FISH) (Vysis ALK Break Apart FISH Probe Kit, Abbott) and next-generation sequencing (NGS) (OseqTMLung Cancer Gene Detection, BGI, China) was performed for cases showed ALK (D5F3) IHC heterogeneity.
Result
ALK (D5F3) double-blind review analysis showed 201 (9.0%) ALK-positive cases, 10 (0.4%) ALK-heterogeneous cases, and 2017 (90.5%) ALK-negative cases. The heterogeneity cases included 2 large cell neuroendocrine carcinomas, 1 lymphoid epithelioid carcinoma, and 7 squamous cell carcinomas. The percentages of tumor cells with strong granular cytoplasmic staining were 1% to 30%. The ALK FISH break apart signal of these ten cases were 0% to 12%, indicating ALK FISH negativity. Nine ALK-heterogeneous cases were successfully detected by NGS, and no ALKgene variations (including gene fusion, copy number variation, insertion/deletion or single nucleotide variation) were found. Immunohistochemical staining showed that some ALK-heterogeneous cases showed neuroendocrine differentiation.
Table. Comparison of IHC, FISH and NGS results of the ALK-heterogeneous cases. ALK
IHC
ALK
FISH
ALK
FISH
ALK
NGS
ALK
NGS
Case No. Gender Age Biopsy/surgery Diagnosis Tumor cell
content
Strong positive staining tumor cells Break apart signal Interpretation result ALK fusion ALK INDEL/SNV/CNV 8thTNM 1 M 69 Wedge resection Large cell neuroendocrine carcinoma 70% 2% 0% Negative Negative Negative pT1bN0M0 2 M 55 Lobectomy Large cell neuroendocrine carcinoma 85% 20% 4% Negative Negative Negative pT2bN0M0 3 F 33 Lobectomy Lymphoid epithelioid carcinoma 60% 5% 0% Negative Negative Negative pT3N0M0 4 M 68 Lobectomy Squamous cell carcinoma 70% 5% 6% Negative Negative Negative pT3N0M0 5 M 69 Lobectomy Squamous cell carcinoma 70% 5% 12% Negative Negative Negative pT2aN0M0
6 M 52 Lobectomy Squamous cell carcinoma 80% 1% 0% Negative Negative Negative pT2aN1M0 7 M 73 Lobectomy Squamous cell carcinoma 90% 5% 2% Negative Negative Negative pT3N0M0 8 M 70 Lobectomy Squamous cell carcinoma 80% 5% 4% Negative Negative Negative pT2bN1M0 9 M 69 Biopsy Squamous cell carcinoma 85% 15% 0% Negative Negative Negative sT3N1M0 10 M 60 Biopsy Squamous cell carcinoma 85% 30% 0% Negative NA NA cT2bN3M0 Abbreviations: INDEL, insertion and deletion; SNV, single nucleotide variation; CNV, copy number variation; NA, NGS was not performed due to insufficient tumor tissues.
Conclusion
Multi-platform detection of ALK-heterogeneous cases did not show evidence of ALKgene variation, and the effect of ALK-TKI treatment was unknown. therefore, the VENTANA ALK scoring interpretation guide for non-small cell lung carcinoma should be revised. It is recommended that ALK-heterogeneous cases be defined as ALK (D5F3) uncertain equivocal cases. The molecular pathology report should clearly state that the clinical significance is unclear, and it is recommended to conduct further testing by FISH or NGS.
