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World J Surg Oncol
2021 Sep 16;191:278. doi: 10.1186/s12957-021-02386-0.
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Pathological cytomorphologic features and the percentage of ALK FISH-positive cells predict pulmonary adenocarcinoma prognosis: a prospective cohort study.
Jiang F
,
Wang C
,
Yang P
,
Sun P
,
Liu J
.
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BACKGROUND: We conducted a study to explore the relationship between pathological cytomorphologic features and the percentage of anaplastic lymphoma kinase (ALK)-positive cells to better predict pulmonary adenocarcinoma prognosis with crizotinib treatment.
PATIENTS AND METHODS: We investigated 60 cases of patients with ALK-positive advanced or metastatic non-small cell lung cancer (NSCLC). Immunohistochemistry was performed to screen for ALK rearrangement. Fluorescence in situ hybridization (FISH) was used to detect the percentage of ALK-positive cells. The primary objectives of the study were the progression-free survival (PFS), the 3-year overall survival, and the 3-year overall survival (OS) rates. The secondary objectives of the study were the disease control rate (DCR) and the overall response rate (ORR).
RESULTS: We compared the pathological cytomorphologic features of 60 cases of ALK-positive pulmonary adenocarcinoma, of which 21 cases were ALK-positive with signet ring cell cytomorphologic characteristics. There were statistical differences in the ORR (p = 0.019), DCR (p = 0.032), and PFS (p = 0.047) between the signet ring cell group and group without signet ring cells. Of these, 37 cases were ALK-positive with EML4 (echinoderm microtubule associated protein like 4)-ALK high percentage of positivity group. These cases benefited more from crizotinib treatment in the ORR (p = 0.046) and achieved a longer PFS (p = 0.036) compared to those with EML4-ALK low percentage of positivity group.
CONCLUSIONS: Signet ring cell cytomorphologic characteristics of pulmonary adenocarcinoma are associated with the percentage of ALK-positive cells. Signet ring cell cytomorphologic characteristics and the percentage of ALK-positive cells might predict the prognosis of pulmonary adenocarcinoma with crizotinib treatment.
TRIAL REGISTRATION: The study was approved by the Institutional Review Board (Medical Ethics Committee of Yantai Yuhuangding Hospital). The registration number is NO.2016[193].
Fig. 1. Cytomorphologic of lung adenocarcinomas harboring ALK rearrangements. a ALK-rearranged lung adenocarcinoma (× 200). b ALK-rearranged lung adenocarcinoma with signet ring cells (red arrows indicate signet ring cells) (× 400). c
ALK-rearranged lung adenocarcinoma with extracellular mucin (× 100). d ALK-rearranged lung adenocarcinoma with cribriform pattern (× 100)
Fig. 2. Comparison of PFS (a) and OS (b) in patients with signet ring cells vs without signet ring cells
Fig. 3. Comparison of PFS (a) and OS (b) in patients with ALK FISH ≥ 50% positive nuclei vs. < 50% positive nuclei
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