{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:10:31Z","timestamp":1791274231226,"version":"4.1.0"},"reference-count":26,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2023,5,10]],"date-time":"2023-05-10T00:00:00Z","timestamp":1683676800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>This study aimed to improve the understanding of the prognostic value of tumor mitotic rate (TMR) in cutaneous melanoma and assessed its significance as a predictor for overall, melanoma\u2010specific, and recurrence\u2010free survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and Methods<\/jats:title>\n                    <jats:p>This is a retrospective multicenter Italian cohort study of 13,016 patients diagnosed with and treated for invasive primary melanoma between 2005 and 2020 with median follow\u2010up of 5.5 years. The survival probability was assessed by Kaplan\u2013Meier method, hazard ratios (HRs), and corresponding 95% confidence interval (CI) of all\u2010cause mortality and recurrence\/death by multivariable Cox proportional hazards models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Higher dermal mitoses number was associated with decreased overall survival. Among patients with TMR 0\/mm\n                      <jats:sup>2<\/jats:sup>\n                      , 1\/mm\n                      <jats:sup>2<\/jats:sup>\n                      , 2\/mm\n                      <jats:sup>2<\/jats:sup>\n                      \u20133\/mm\n                      <jats:sup>2<\/jats:sup>\n                      , 4\/mm\n                      <jats:sup>2<\/jats:sup>\n                      \u201310\/mm\n                      <jats:sup>2<\/jats:sup>\n                      , and &gt;10\/mm\n                      <jats:sup>2<\/jats:sup>\n                      , 5\u2010year overall survival (OS) was 97.3%, 93.6%, 88.3%, 73.0%, and 60.9%, respectively. In multivariate analyses, compared to TMR of 0\/mm\n                      <jats:sup>2<\/jats:sup>\n                      , HRs for all\u2010cause mortality were 1.35 (95% CI, 1.08\u20131.68), 1.70 (95% CI, 1.40\u20132.07), 2.04 (95% CI, 1.67\u20132.49), and 2.39 (95% CI, 1.90\u20133.00) for 1 mitoses\/mm\n                      <jats:sup>2<\/jats:sup>\n                      , 2 mitoses\/mm\n                      <jats:sup>2<\/jats:sup>\n                      \u20133 mitoses\/mm\n                      <jats:sup>2<\/jats:sup>\n                      , 4 mitoses\/mm\n                      <jats:sup>2<\/jats:sup>\n                      \u201310 mitoses\/mm\n                      <jats:sup>2<\/jats:sup>\n                      , and &gt;10 mitoses\/mm\n                      <jats:sup>2<\/jats:sup>\n                      , respectively. A similar increase in risks was observed in melanoma\u2010specific survival (MSS) and recurrence\u2010free survival (RFS). The HRs for MSS and RFS for the highest compared to the lowest TMR category were 3.01 (95% CI, 2.20\u20134.11) and 2.26 (95% CI, 1.88\u20132.73), respectively. Sentinel lymph\u2010node biopsy positivity was significantly associated with TMR increase even with adjustment for several potential confounders.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>A clear association was demonstrated between an increasing TMR and decreased OS, MSS, and RFS, suggesting a reconsideration of TMR prognostic role for future inclusion in the melanoma staging system.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Plain Language Summary<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>The 8th American Joint Committee on Cancer for melanoma staging removed tumor mitotic rate (TMR) from the staging criteria for T1 melanomas, giving way to ulceration and tumor thickness as stronger prognostic predictors.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>However, it is still recommended that TMR should be assessed and recorded in all primary invasive melanomas.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>In a large retrospective multicenter study on primary invasive melanomas, we investigated the prognostic value of TMR to assess its significance as survival predictor.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Our results showed a clear association between increasing TMR and decreased patients' survival, suggesting that TMR should be considered for inclusion in the melanoma staging system.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n 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