open access publication

Article, 2024

Prognostic Thresholds of Mitotic Count and Ki-67 Labeling Index for Recurrence and Survival in Lung Atypical Carcinoids

Cancers, ISSN 2072-6694, Volume 16, 3, Page 502, 10.3390/cancers16030502

Contributors

Soldath, Patrick 0000-0002-5275-1661 (Corresponding author) [1] [2] [3] Bianchi, Daniel [4] Manfredini, Beatrice 0009-0001-9932-5117 [5] [6] Kjaer, Andreas 0000-0002-2706-5547 [1] [2] [3] Langer, Seppo Wang 0000-0002-3467-7023 [1] [2] [3] Knigge, Ulrich Peter [1] [2] Melfi, Franca Maria Antonietta 0000-0002-1773-8269 [5] [6] Filosso, Pier Luigi 0000-0002-1210-307X [4] Petersen, René Horsleben 0000-0002-3586-1869 [1] [2] [3]

Affiliations

  1. [1] European Neuroendocrine Tumor Society Center of Excellence, Copenhagen University Hospital-Rigshospitalet, 2100 Copenhagen, Denmark;, andreas.kjaer@regionh.dk, (A.K.);, seppo.langer@regionh.dk, (S.W.L.);, ulrich.peter.knigge@regionh.dk, (U.K.);, rene.horsleben.petersen@regionh.dk, (R.H.P.)
  2. [NORA names: United Kingdom; Europe, Non-EU; OECD];
  3. [2] Rigshospitalet
  4. [NORA names: Capital Region of Denmark; Hospital; Denmark; Europe, EU; Nordic; OECD];
  5. [3] University of Copenhagen
  6. [NORA names: KU University of Copenhagen; University; Denmark; Europe, EU; Nordic; OECD];
  7. [4] University of Modena and Reggio Emilia
  8. [NORA names: Italy; Europe, EU; OECD];
  9. [5] Minimally Invasive and Robotic Thoracic Surgery, Surgical, Medical, Molecular, and Critical Care Pathology Department, University of Pisa, 56126 Pisa, Italy;, beatrice.manfredini91@gmail.com, (B.M.);, franca.melfi@unipi.it, (F.M.)

Abstract

Atypical carcinoid (AC) is a rare neuroendocrine neoplasm of the lung, which exhibits a varying malignant potential. In this study, we aimed to identify the prognostic thresholds of the mitotic count and Ki-67 labeling index for recurrence and survival in AC. We retrospectively reviewed 78 patients who had been radically resected for AC and calculated said thresholds using time-dependent receiver operating characteristic curves and the Youden index. We then dichotomized the patients into groups of above or below these thresholds and estimated the cumulative incidences of the groups using the Aalen-Johansen estimator. We compared the groups using univariable and multivariable Fine-Gray subdistribution hazard models. Our findings show that more patients recurred and died from this disease if their mitotic count exceeded three and four mitoses per 2 mm2, respectively, or if their Ki-67 labeling index exceeded 14% and 11%, respectively. Both thresholds independently predicted survival (p < 0.001 and p = 0.015, respectively). These thresholds may serve as a valuable tool for clinicians and researchers in making treatment plans and predicting outcomes for patients with AC.

Keywords

Aalen-Johansen, Aalen-Johansen estimator, Fine-Gray subdistribution hazard model, Ki-67, Ki-67 labeling index, Youden, Youden index, atypical carcinoid, carcinoid, characteristic curve, clinicians, count, cumulative incidence, curves, disease, estimation, findings, group, hazards model, incidence, index, labeling index, lung, malignant potential, mitoses, mitotic count, model, neoplasms, neuroendocrine neoplasms, outcomes, patients, planning, potential, predicting outcome, predicting survival, prognostic threshold, rare neuroendocrine neoplasm, receiver operating characteristic curve, recurrence, research, study, subdistribution hazard model, survival, threshold, time-dependent receiver operating characteristic curve, treatment, treatment planning

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