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Clinicopathological predictors of recurrence in nodular and superficial spreading cutaneous melanoma: a multivariate analysis of 214 cases
Nodular melanoma (NM) accounts for most thick melanomas and because of their frequent association with ulceration, fast growth rate and high mitotic rate, contribute substantially to melanoma-related mortality. In a multicentric series of 214 primary melanomas including 96 NM and 118 superficial spr...
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Published in: | Journal of translational medicine 2017-11, Vol.15 (1), p.227-227, Article 227 |
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creator | Pizzichetta, Maria A Massi, Daniela Mandalà, Mario Queirolo, Paola Stanganelli, Ignazio De Giorgi, Vincenzo Ghigliotti, Giovanni Cavicchini, Stefano Quaglino, Pietro Corradin, Maria T Rubegni, Pietro Alaibac, Mauro Astorino, Stefano Ayala, Fabrizio Magi, Serena Mazzoni, Laura Manganoni, Maria Ausilia Talamini, Renato Serraino, Diego Palmieri, Giuseppe |
description | Nodular melanoma (NM) accounts for most thick melanomas and because of their frequent association with ulceration, fast growth rate and high mitotic rate, contribute substantially to melanoma-related mortality. In a multicentric series of 214 primary melanomas including 96 NM and 118 superficial spreading melanoma (SSM), histopathological features were examined with the aim to identify clinicopathological predictors of recurrence.
All consecutive cases of histopathologically diagnosed primary invasive SSM and NM during the period 2005-2010, were retrieved from the 12 participating Italian Melanoma Intergroup (IMI) centers. Each center provided clinico-pathological data such as gender, age at diagnosis, anatomical site, histopathological conventional parameters, date of excision and first melanoma recurrence.
Results showed that NM subtype was significantly associated with Breslow thickness (BT) at multivariate analysis: [BT 1.01-2 mm (OR 7.22; 95% CI 2.73-19.05), BT 2.01-4 mm (OR 7.04; 95% CI 2.54-19.56), and BT > 4 mm (OR 51.78; 95% CI 5.65-474.86) (p 5 mitoses/mm
(OR 4.87; 95% CI 1.77-13.40) (p = 0.002)]. The risk of recurrence was not significantly associated with NM histotype while BT [BT 1.01-2.00 mm (HR 1.55; 95% CI 0.51-4.71), BT 2.01-4.00 mm (HR 2.42; 95% CI 0.89-6.54), BT > 4.00 mm. (HR 3.13; 95% CI 0.95-10.28) (p = 0.05)], mitotic rate [MR > 2 mitoses/mm
(HR 2.34; 95% CI, 1.11-4.97) (p = 0.03)] and the positivity of lymph node sentinel biopsy (SNLB) (HR 2.60; 95% CI 1.19-5.68) (p = 0.007) were significantly associated with an increased risk of recurrence at multivariate analysis.
We found that NM subtype was significantly associated with higher BT and MR but it was not a prognostic factor since it did not significantly correlate with melanoma recurrence rate. Conversely, increased BT and MR as well as SNLB positivity were significantly associated with a higher risk of melanoma recurrence. |
doi_str_mv | 10.1186/s12967-017-1332-3 |
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All consecutive cases of histopathologically diagnosed primary invasive SSM and NM during the period 2005-2010, were retrieved from the 12 participating Italian Melanoma Intergroup (IMI) centers. Each center provided clinico-pathological data such as gender, age at diagnosis, anatomical site, histopathological conventional parameters, date of excision and first melanoma recurrence.
Results showed that NM subtype was significantly associated with Breslow thickness (BT) at multivariate analysis: [BT 1.01-2 mm (OR 7.22; 95% CI 2.73-19.05), BT 2.01-4 mm (OR 7.04; 95% CI 2.54-19.56), and BT > 4 mm (OR 51.78; 95% CI 5.65-474.86) (p < 0.0001)]. Furthermore, mitotic rate (MR) was significantly correlated with NM histotype: [(MR 3-5 mitoses/mm
(OR 2.62; 95% CI 1.01-6.83) and MR > 5 mitoses/mm
(OR 4.87; 95% CI 1.77-13.40) (p = 0.002)]. The risk of recurrence was not significantly associated with NM histotype while BT [BT 1.01-2.00 mm (HR 1.55; 95% CI 0.51-4.71), BT 2.01-4.00 mm (HR 2.42; 95% CI 0.89-6.54), BT > 4.00 mm. (HR 3.13; 95% CI 0.95-10.28) (p = 0.05)], mitotic rate [MR > 2 mitoses/mm
(HR 2.34; 95% CI, 1.11-4.97) (p = 0.03)] and the positivity of lymph node sentinel biopsy (SNLB) (HR 2.60; 95% CI 1.19-5.68) (p = 0.007) were significantly associated with an increased risk of recurrence at multivariate analysis.
We found that NM subtype was significantly associated with higher BT and MR but it was not a prognostic factor since it did not significantly correlate with melanoma recurrence rate. Conversely, increased BT and MR as well as SNLB positivity were significantly associated with a higher risk of melanoma recurrence.</description><identifier>ISSN: 1479-5876</identifier><identifier>EISSN: 1479-5876</identifier><identifier>DOI: 10.1186/s12967-017-1332-3</identifier><identifier>PMID: 29115977</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Adolescent ; Adult ; Aged ; Aged, 80 and over ; Analysis ; Development and progression ; Diagnosis ; Female ; Health aspects ; Humans ; Lymphatic Metastasis - pathology ; Male ; Melanoma ; Melanoma - pathology ; Melanoma, Cutaneous Malignant ; Middle Aged ; Mortality ; Multivariate Analysis ; Neoplasm Recurrence, Local - pathology ; Nodular melanoma ; Probability ; Prognostic indicators ; Recurrence ; Recurrence (Disease) ; Risk factors ; Skin Neoplasms - pathology ; Superficial spreading melanoma ; Young Adult</subject><ispartof>Journal of translational medicine, 2017-11, Vol.15 (1), p.227-227, Article 227</ispartof><rights>COPYRIGHT 2017 BioMed Central Ltd.</rights><rights>The Author(s) 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c532t-1c0a672160e66263373b7e4c920cacb49484bbf264010c9424fd84fa23b9cb213</citedby><cites>FETCH-LOGICAL-c532t-1c0a672160e66263373b7e4c920cacb49484bbf264010c9424fd84fa23b9cb213</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5688807/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5688807/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,37013,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29115977$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pizzichetta, Maria A</creatorcontrib><creatorcontrib>Massi, Daniela</creatorcontrib><creatorcontrib>Mandalà, Mario</creatorcontrib><creatorcontrib>Queirolo, Paola</creatorcontrib><creatorcontrib>Stanganelli, Ignazio</creatorcontrib><creatorcontrib>De Giorgi, Vincenzo</creatorcontrib><creatorcontrib>Ghigliotti, Giovanni</creatorcontrib><creatorcontrib>Cavicchini, Stefano</creatorcontrib><creatorcontrib>Quaglino, Pietro</creatorcontrib><creatorcontrib>Corradin, Maria T</creatorcontrib><creatorcontrib>Rubegni, Pietro</creatorcontrib><creatorcontrib>Alaibac, Mauro</creatorcontrib><creatorcontrib>Astorino, Stefano</creatorcontrib><creatorcontrib>Ayala, Fabrizio</creatorcontrib><creatorcontrib>Magi, Serena</creatorcontrib><creatorcontrib>Mazzoni, Laura</creatorcontrib><creatorcontrib>Manganoni, Maria Ausilia</creatorcontrib><creatorcontrib>Talamini, Renato</creatorcontrib><creatorcontrib>Serraino, Diego</creatorcontrib><creatorcontrib>Palmieri, Giuseppe</creatorcontrib><creatorcontrib>Italian Melanoma Intergroup (IMI)</creatorcontrib><creatorcontrib>on behalf of the Italian Melanoma Intergroup (IMI)</creatorcontrib><title>Clinicopathological predictors of recurrence in nodular and superficial spreading cutaneous melanoma: a multivariate analysis of 214 cases</title><title>Journal of translational medicine</title><addtitle>J Transl Med</addtitle><description>Nodular melanoma (NM) accounts for most thick melanomas and because of their frequent association with ulceration, fast growth rate and high mitotic rate, contribute substantially to melanoma-related mortality. In a multicentric series of 214 primary melanomas including 96 NM and 118 superficial spreading melanoma (SSM), histopathological features were examined with the aim to identify clinicopathological predictors of recurrence.
All consecutive cases of histopathologically diagnosed primary invasive SSM and NM during the period 2005-2010, were retrieved from the 12 participating Italian Melanoma Intergroup (IMI) centers. Each center provided clinico-pathological data such as gender, age at diagnosis, anatomical site, histopathological conventional parameters, date of excision and first melanoma recurrence.
Results showed that NM subtype was significantly associated with Breslow thickness (BT) at multivariate analysis: [BT 1.01-2 mm (OR 7.22; 95% CI 2.73-19.05), BT 2.01-4 mm (OR 7.04; 95% CI 2.54-19.56), and BT > 4 mm (OR 51.78; 95% CI 5.65-474.86) (p < 0.0001)]. Furthermore, mitotic rate (MR) was significantly correlated with NM histotype: [(MR 3-5 mitoses/mm
(OR 2.62; 95% CI 1.01-6.83) and MR > 5 mitoses/mm
(OR 4.87; 95% CI 1.77-13.40) (p = 0.002)]. The risk of recurrence was not significantly associated with NM histotype while BT [BT 1.01-2.00 mm (HR 1.55; 95% CI 0.51-4.71), BT 2.01-4.00 mm (HR 2.42; 95% CI 0.89-6.54), BT > 4.00 mm. (HR 3.13; 95% CI 0.95-10.28) (p = 0.05)], mitotic rate [MR > 2 mitoses/mm
(HR 2.34; 95% CI, 1.11-4.97) (p = 0.03)] and the positivity of lymph node sentinel biopsy (SNLB) (HR 2.60; 95% CI 1.19-5.68) (p = 0.007) were significantly associated with an increased risk of recurrence at multivariate analysis.
We found that NM subtype was significantly associated with higher BT and MR but it was not a prognostic factor since it did not significantly correlate with melanoma recurrence rate. Conversely, increased BT and MR as well as SNLB positivity were significantly associated with a higher risk of melanoma recurrence.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Analysis</subject><subject>Development and progression</subject><subject>Diagnosis</subject><subject>Female</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Lymphatic Metastasis - pathology</subject><subject>Male</subject><subject>Melanoma</subject><subject>Melanoma - pathology</subject><subject>Melanoma, Cutaneous Malignant</subject><subject>Middle Aged</subject><subject>Mortality</subject><subject>Multivariate Analysis</subject><subject>Neoplasm Recurrence, Local - pathology</subject><subject>Nodular melanoma</subject><subject>Probability</subject><subject>Prognostic indicators</subject><subject>Recurrence</subject><subject>Recurrence (Disease)</subject><subject>Risk factors</subject><subject>Skin Neoplasms - pathology</subject><subject>Superficial spreading melanoma</subject><subject>Young Adult</subject><issn>1479-5876</issn><issn>1479-5876</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>DOA</sourceid><recordid>eNptks1q3TAQhU1padK0D9BNEXTTjVP9WbK7KIRLfwKBbtq1GI9lR0GWbiU7kFfoU1c3TkMuFC0kRnM-jjSnqt4yes5Yqz5mxjula8p0zYTgtXhWnTKpu7pptXr-5HxSvcr5hlIuG9m9rE54x1jTaX1a_dl5FxzGPSzX0cfJIXiyT3ZwuMSUSRxJsrimZANa4gIJcVg9JAJhIHnd2zQ6dEWTiwgGFyaC6wLBxjWT2XoIcYZPBMi8-sXdQnKw2CIGf5fdPZ4zSRCyza-rFyP4bN887GfVr69ffu6-11c_vl3uLq5qbARfaoYUlOZMUasUV0Jo0WsrseMUAXvZyVb2_ciVpIxiJ7kch1aOwEXfYc-ZOKsuN-4Q4cbsk5sh3ZkIztwXYpoMpMWht4Z1vG36rm3bBiXqvkdrW6naQYmxoWoorM8ba7_2sx3QhiWBP4Ie3wR3baZ4axpVoFQXwIcHQIq_V5sXM7uM1vvtC4sDVSZd5nbw_X5rnaBYc2GMhYiHdnPRCMGE1k1bus7_01XWYOcy52BHV-pHArYJMMWckx0f3TNqDjEzW8xMiZk5xMyIonn39NmPin-5En8B5mnPUg</recordid><startdate>20171107</startdate><enddate>20171107</enddate><creator>Pizzichetta, Maria A</creator><creator>Massi, Daniela</creator><creator>Mandalà, Mario</creator><creator>Queirolo, Paola</creator><creator>Stanganelli, Ignazio</creator><creator>De Giorgi, Vincenzo</creator><creator>Ghigliotti, Giovanni</creator><creator>Cavicchini, Stefano</creator><creator>Quaglino, Pietro</creator><creator>Corradin, Maria T</creator><creator>Rubegni, Pietro</creator><creator>Alaibac, Mauro</creator><creator>Astorino, Stefano</creator><creator>Ayala, Fabrizio</creator><creator>Magi, Serena</creator><creator>Mazzoni, Laura</creator><creator>Manganoni, Maria Ausilia</creator><creator>Talamini, Renato</creator><creator>Serraino, Diego</creator><creator>Palmieri, Giuseppe</creator><general>BioMed Central Ltd</general><general>BioMed Central</general><general>BMC</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20171107</creationdate><title>Clinicopathological predictors of recurrence in nodular and superficial spreading cutaneous melanoma: a multivariate analysis of 214 cases</title><author>Pizzichetta, Maria A ; Massi, Daniela ; Mandalà, Mario ; Queirolo, Paola ; Stanganelli, Ignazio ; De Giorgi, Vincenzo ; Ghigliotti, Giovanni ; Cavicchini, Stefano ; Quaglino, Pietro ; Corradin, Maria T ; Rubegni, Pietro ; Alaibac, Mauro ; Astorino, Stefano ; Ayala, Fabrizio ; Magi, Serena ; Mazzoni, Laura ; Manganoni, Maria Ausilia ; Talamini, Renato ; Serraino, Diego ; Palmieri, Giuseppe</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c532t-1c0a672160e66263373b7e4c920cacb49484bbf264010c9424fd84fa23b9cb213</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Analysis</topic><topic>Development and progression</topic><topic>Diagnosis</topic><topic>Female</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Lymphatic Metastasis - pathology</topic><topic>Male</topic><topic>Melanoma</topic><topic>Melanoma - pathology</topic><topic>Melanoma, Cutaneous Malignant</topic><topic>Middle Aged</topic><topic>Mortality</topic><topic>Multivariate Analysis</topic><topic>Neoplasm Recurrence, Local - pathology</topic><topic>Nodular melanoma</topic><topic>Probability</topic><topic>Prognostic indicators</topic><topic>Recurrence</topic><topic>Recurrence (Disease)</topic><topic>Risk factors</topic><topic>Skin Neoplasms - pathology</topic><topic>Superficial spreading melanoma</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pizzichetta, Maria A</creatorcontrib><creatorcontrib>Massi, Daniela</creatorcontrib><creatorcontrib>Mandalà, Mario</creatorcontrib><creatorcontrib>Queirolo, Paola</creatorcontrib><creatorcontrib>Stanganelli, Ignazio</creatorcontrib><creatorcontrib>De Giorgi, Vincenzo</creatorcontrib><creatorcontrib>Ghigliotti, Giovanni</creatorcontrib><creatorcontrib>Cavicchini, Stefano</creatorcontrib><creatorcontrib>Quaglino, Pietro</creatorcontrib><creatorcontrib>Corradin, Maria T</creatorcontrib><creatorcontrib>Rubegni, Pietro</creatorcontrib><creatorcontrib>Alaibac, Mauro</creatorcontrib><creatorcontrib>Astorino, Stefano</creatorcontrib><creatorcontrib>Ayala, Fabrizio</creatorcontrib><creatorcontrib>Magi, Serena</creatorcontrib><creatorcontrib>Mazzoni, Laura</creatorcontrib><creatorcontrib>Manganoni, Maria Ausilia</creatorcontrib><creatorcontrib>Talamini, Renato</creatorcontrib><creatorcontrib>Serraino, Diego</creatorcontrib><creatorcontrib>Palmieri, Giuseppe</creatorcontrib><creatorcontrib>Italian Melanoma Intergroup (IMI)</creatorcontrib><creatorcontrib>on behalf of the Italian Melanoma Intergroup (IMI)</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Directory of Open Access Journals</collection><jtitle>Journal of translational medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pizzichetta, Maria A</au><au>Massi, Daniela</au><au>Mandalà, Mario</au><au>Queirolo, Paola</au><au>Stanganelli, Ignazio</au><au>De Giorgi, Vincenzo</au><au>Ghigliotti, Giovanni</au><au>Cavicchini, Stefano</au><au>Quaglino, Pietro</au><au>Corradin, Maria T</au><au>Rubegni, Pietro</au><au>Alaibac, Mauro</au><au>Astorino, Stefano</au><au>Ayala, Fabrizio</au><au>Magi, Serena</au><au>Mazzoni, Laura</au><au>Manganoni, Maria Ausilia</au><au>Talamini, Renato</au><au>Serraino, Diego</au><au>Palmieri, Giuseppe</au><aucorp>Italian Melanoma Intergroup (IMI)</aucorp><aucorp>on behalf of the Italian Melanoma Intergroup (IMI)</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Clinicopathological predictors of recurrence in nodular and superficial spreading cutaneous melanoma: a multivariate analysis of 214 cases</atitle><jtitle>Journal of translational medicine</jtitle><addtitle>J Transl Med</addtitle><date>2017-11-07</date><risdate>2017</risdate><volume>15</volume><issue>1</issue><spage>227</spage><epage>227</epage><pages>227-227</pages><artnum>227</artnum><issn>1479-5876</issn><eissn>1479-5876</eissn><abstract>Nodular melanoma (NM) accounts for most thick melanomas and because of their frequent association with ulceration, fast growth rate and high mitotic rate, contribute substantially to melanoma-related mortality. In a multicentric series of 214 primary melanomas including 96 NM and 118 superficial spreading melanoma (SSM), histopathological features were examined with the aim to identify clinicopathological predictors of recurrence.
All consecutive cases of histopathologically diagnosed primary invasive SSM and NM during the period 2005-2010, were retrieved from the 12 participating Italian Melanoma Intergroup (IMI) centers. Each center provided clinico-pathological data such as gender, age at diagnosis, anatomical site, histopathological conventional parameters, date of excision and first melanoma recurrence.
Results showed that NM subtype was significantly associated with Breslow thickness (BT) at multivariate analysis: [BT 1.01-2 mm (OR 7.22; 95% CI 2.73-19.05), BT 2.01-4 mm (OR 7.04; 95% CI 2.54-19.56), and BT > 4 mm (OR 51.78; 95% CI 5.65-474.86) (p < 0.0001)]. Furthermore, mitotic rate (MR) was significantly correlated with NM histotype: [(MR 3-5 mitoses/mm
(OR 2.62; 95% CI 1.01-6.83) and MR > 5 mitoses/mm
(OR 4.87; 95% CI 1.77-13.40) (p = 0.002)]. The risk of recurrence was not significantly associated with NM histotype while BT [BT 1.01-2.00 mm (HR 1.55; 95% CI 0.51-4.71), BT 2.01-4.00 mm (HR 2.42; 95% CI 0.89-6.54), BT > 4.00 mm. (HR 3.13; 95% CI 0.95-10.28) (p = 0.05)], mitotic rate [MR > 2 mitoses/mm
(HR 2.34; 95% CI, 1.11-4.97) (p = 0.03)] and the positivity of lymph node sentinel biopsy (SNLB) (HR 2.60; 95% CI 1.19-5.68) (p = 0.007) were significantly associated with an increased risk of recurrence at multivariate analysis.
We found that NM subtype was significantly associated with higher BT and MR but it was not a prognostic factor since it did not significantly correlate with melanoma recurrence rate. Conversely, increased BT and MR as well as SNLB positivity were significantly associated with a higher risk of melanoma recurrence.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>29115977</pmid><doi>10.1186/s12967-017-1332-3</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adolescent Adult Aged Aged, 80 and over Analysis Development and progression Diagnosis Female Health aspects Humans Lymphatic Metastasis - pathology Male Melanoma Melanoma - pathology Melanoma, Cutaneous Malignant Middle Aged Mortality Multivariate Analysis Neoplasm Recurrence, Local - pathology Nodular melanoma Probability Prognostic indicators Recurrence Recurrence (Disease) Risk factors Skin Neoplasms - pathology Superficial spreading melanoma Young Adult |
title | Clinicopathological predictors of recurrence in nodular and superficial spreading cutaneous melanoma: a multivariate analysis of 214 cases |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-05T08%3A19%3A09IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_doaj_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Clinicopathological%20predictors%20of%20recurrence%20in%20nodular%20and%20superficial%20spreading%20cutaneous%20melanoma:%20a%20multivariate%20analysis%20of%20214%20cases&rft.jtitle=Journal%20of%20translational%20medicine&rft.au=Pizzichetta,%20Maria%20A&rft.aucorp=Italian%20Melanoma%20Intergroup%20(IMI)&rft.date=2017-11-07&rft.volume=15&rft.issue=1&rft.spage=227&rft.epage=227&rft.pages=227-227&rft.artnum=227&rft.issn=1479-5876&rft.eissn=1479-5876&rft_id=info:doi/10.1186/s12967-017-1332-3&rft_dat=%3Cgale_doaj_%3EA533137758%3C/gale_doaj_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c532t-1c0a672160e66263373b7e4c920cacb49484bbf264010c9424fd84fa23b9cb213%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1961862451&rft_id=info:pmid/29115977&rft_galeid=A533137758&rfr_iscdi=true |