Evaluation of T‐lymphocyte subpopulations in actinic keratosis, in situ and invasive squamous cell carcinoma of the skin
Background Tumor infiltrating lymphocytes (TILs) represent important regulators of carcinogenesis. Cutaneous invasive squamous cell carcinoma (inSCC) develops through precursor lesions, namely in situ squamous cell carcinoma (isSCC) and actinic keratosis (AK), representing a natural model of carcino...
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Veröffentlicht in: | Journal of cutaneous pathology 2018-05, Vol.45 (5), p.337-347 |
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description | Background
Tumor infiltrating lymphocytes (TILs) represent important regulators of carcinogenesis. Cutaneous invasive squamous cell carcinoma (inSCC) develops through precursor lesions, namely in situ squamous cell carcinoma (isSCC) and actinic keratosis (AK), representing a natural model of carcinogenesis. The study evaluates TIL subpopulations in inSCC and its precursors by comparing 2 semiquantitative scoring systems, and assesses the presence of regulatory T‐cells (Tregs) in these lesions.
Methods
Paraffin sections from 33 cases of AK, 19 isSCCs and 34 inSCCs with adjacent precursor lesions or normal skin (NS) were immunostained for CD3, CD4, CD8 and Foxp3. TIL subgroups were evaluated by the semiquantitative Klintrup‐Mäkinen (K‐M) score, and by a more detailed modification of this system. Treg counts were assessed by image analysis quantification.
Results
An increase of all TIL subpolulations from precursor lesions toward inSCC was shown by both scoring systems. Treg counts progressively increased from NS to AK and isSCC, but decreased in inSCC. Tregs were more numerous in pT2 and around indolent inSCCs compared to T1 and aggressive subtypes.
Conclusions
T‐cells and cytotoxic T‐cells progressively increase in cutaneous squamous cell carcinogenesis, while Treg counts diminish in inSCC. The K‐M score is an appropriate, easily applicable TIL scoring system in cutaneous inSCC. |
doi_str_mv | 10.1111/cup.13123 |
format | Article |
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Tumor infiltrating lymphocytes (TILs) represent important regulators of carcinogenesis. Cutaneous invasive squamous cell carcinoma (inSCC) develops through precursor lesions, namely in situ squamous cell carcinoma (isSCC) and actinic keratosis (AK), representing a natural model of carcinogenesis. The study evaluates TIL subpopulations in inSCC and its precursors by comparing 2 semiquantitative scoring systems, and assesses the presence of regulatory T‐cells (Tregs) in these lesions.
Methods
Paraffin sections from 33 cases of AK, 19 isSCCs and 34 inSCCs with adjacent precursor lesions or normal skin (NS) were immunostained for CD3, CD4, CD8 and Foxp3. TIL subgroups were evaluated by the semiquantitative Klintrup‐Mäkinen (K‐M) score, and by a more detailed modification of this system. Treg counts were assessed by image analysis quantification.
Results
An increase of all TIL subpolulations from precursor lesions toward inSCC was shown by both scoring systems. Treg counts progressively increased from NS to AK and isSCC, but decreased in inSCC. Tregs were more numerous in pT2 and around indolent inSCCs compared to T1 and aggressive subtypes.
Conclusions
T‐cells and cytotoxic T‐cells progressively increase in cutaneous squamous cell carcinogenesis, while Treg counts diminish in inSCC. The K‐M score is an appropriate, easily applicable TIL scoring system in cutaneous inSCC.</description><identifier>ISSN: 0303-6987</identifier><identifier>EISSN: 1600-0560</identifier><identifier>DOI: 10.1111/cup.13123</identifier><identifier>PMID: 29419888</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>actinic keratosis ; Aged ; Aged, 80 and over ; Carcinogenesis ; Carcinoma in Situ - immunology ; Carcinoma in Situ - pathology ; Carcinoma, Squamous Cell - immunology ; Carcinoma, Squamous Cell - pathology ; CD3 antigen ; CD4 antigen ; CD8 antigen ; Cytotoxicity ; Female ; Foxp3 protein ; Humans ; Image processing ; in situ squamous cell carcinoma ; invasive squamous cell carcinoma ; Invasiveness ; Keratosis ; Keratosis, Actinic - immunology ; Keratosis, Actinic - pathology ; Lymphocytes ; Lymphocytes T ; Lymphocytes, Tumor-Infiltrating - immunology ; Lymphocytes, Tumor-Infiltrating - pathology ; Male ; Middle Aged ; Paraffin ; Precancerous Conditions - immunology ; Precancerous Conditions - pathology ; regulatory T‐cells (Tregs) ; Retrospective Studies ; Skin diseases ; Skin Neoplasms - immunology ; Skin Neoplasms - pathology ; Squamous cell carcinoma ; T-Lymphocyte Subsets - immunology ; T-Lymphocyte Subsets - pathology ; tumor infiltrating lymphocytes (TILs)</subject><ispartof>Journal of cutaneous pathology, 2018-05, Vol.45 (5), p.337-347</ispartof><rights>2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd</rights><rights>2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3533-f99dc164ef8606d2658c13da0687257d4fc76f8e0deea0d86a615d2c768be35a3</citedby><cites>FETCH-LOGICAL-c3533-f99dc164ef8606d2658c13da0687257d4fc76f8e0deea0d86a615d2c768be35a3</cites><orcidid>0000-0001-8838-8334</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fcup.13123$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fcup.13123$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29419888$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Stravodimou, Aristea</creatorcontrib><creatorcontrib>Tzelepi, Vassiliki</creatorcontrib><creatorcontrib>Papadaki, Helen</creatorcontrib><creatorcontrib>Mouzaki, Athanasia</creatorcontrib><creatorcontrib>Georgiou, Sophia</creatorcontrib><creatorcontrib>Melachrinou, Maria</creatorcontrib><creatorcontrib>Kourea, Eleni P.</creatorcontrib><title>Evaluation of T‐lymphocyte subpopulations in actinic keratosis, in situ and invasive squamous cell carcinoma of the skin</title><title>Journal of cutaneous pathology</title><addtitle>J Cutan Pathol</addtitle><description>Background
Tumor infiltrating lymphocytes (TILs) represent important regulators of carcinogenesis. Cutaneous invasive squamous cell carcinoma (inSCC) develops through precursor lesions, namely in situ squamous cell carcinoma (isSCC) and actinic keratosis (AK), representing a natural model of carcinogenesis. The study evaluates TIL subpopulations in inSCC and its precursors by comparing 2 semiquantitative scoring systems, and assesses the presence of regulatory T‐cells (Tregs) in these lesions.
Methods
Paraffin sections from 33 cases of AK, 19 isSCCs and 34 inSCCs with adjacent precursor lesions or normal skin (NS) were immunostained for CD3, CD4, CD8 and Foxp3. TIL subgroups were evaluated by the semiquantitative Klintrup‐Mäkinen (K‐M) score, and by a more detailed modification of this system. Treg counts were assessed by image analysis quantification.
Results
An increase of all TIL subpolulations from precursor lesions toward inSCC was shown by both scoring systems. Treg counts progressively increased from NS to AK and isSCC, but decreased in inSCC. Tregs were more numerous in pT2 and around indolent inSCCs compared to T1 and aggressive subtypes.
Conclusions
T‐cells and cytotoxic T‐cells progressively increase in cutaneous squamous cell carcinogenesis, while Treg counts diminish in inSCC. The K‐M score is an appropriate, easily applicable TIL scoring system in cutaneous inSCC.</description><subject>actinic keratosis</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Carcinogenesis</subject><subject>Carcinoma in Situ - immunology</subject><subject>Carcinoma in Situ - pathology</subject><subject>Carcinoma, Squamous Cell - immunology</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>CD3 antigen</subject><subject>CD4 antigen</subject><subject>CD8 antigen</subject><subject>Cytotoxicity</subject><subject>Female</subject><subject>Foxp3 protein</subject><subject>Humans</subject><subject>Image processing</subject><subject>in situ squamous cell carcinoma</subject><subject>invasive squamous cell carcinoma</subject><subject>Invasiveness</subject><subject>Keratosis</subject><subject>Keratosis, Actinic - immunology</subject><subject>Keratosis, Actinic - pathology</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Lymphocytes, Tumor-Infiltrating - immunology</subject><subject>Lymphocytes, Tumor-Infiltrating - pathology</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Paraffin</subject><subject>Precancerous Conditions - immunology</subject><subject>Precancerous Conditions - pathology</subject><subject>regulatory T‐cells (Tregs)</subject><subject>Retrospective Studies</subject><subject>Skin diseases</subject><subject>Skin Neoplasms - immunology</subject><subject>Skin Neoplasms - pathology</subject><subject>Squamous cell carcinoma</subject><subject>T-Lymphocyte Subsets - immunology</subject><subject>T-Lymphocyte Subsets - pathology</subject><subject>tumor infiltrating lymphocytes (TILs)</subject><issn>0303-6987</issn><issn>1600-0560</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kE1OwzAQRi0EoqWw4ALIEisk0tpx4zhLVJUfqRIs2nXk2o7qNonTOC4KK47AGTkJblPY4c1YM2--kR4A1xgNsX8j4aohJjgkJ6CPKUIBiig6BX1EEAlowuIeuLB2jRCmjEbnoBcmY5wwxvrgY7rjueONNiU0GZx_f37lbVGtjGgbBa1bVqZy-WFuoS4hF40utYAbVfPGWG3v912rGwd5Kf1_x63e-c2t44VxFgqV51DwWujSFHx_o1n58UaXl-As47lVV8c6AIvH6XzyHMxen14mD7NAkIiQIEsSKTAdq4xRRGVIIyYwkRxRFodRLMeZiGnGFJJKcSQZ5RRHMvRNtlQk4mQAbrvcqjZbp2yTro2rS38yDVHoTYU4jj1111GiNtbWKkurWhe8blOM0r3l1FtOD5Y9e3NMdMtCyT_yV6sHRh3wrnPV_p-UThZvXeQP_EOJYg</recordid><startdate>201805</startdate><enddate>201805</enddate><creator>Stravodimou, Aristea</creator><creator>Tzelepi, Vassiliki</creator><creator>Papadaki, Helen</creator><creator>Mouzaki, Athanasia</creator><creator>Georgiou, Sophia</creator><creator>Melachrinou, Maria</creator><creator>Kourea, Eleni P.</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</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>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>H94</scope><orcidid>https://orcid.org/0000-0001-8838-8334</orcidid></search><sort><creationdate>201805</creationdate><title>Evaluation of T‐lymphocyte subpopulations in actinic keratosis, in situ and invasive squamous cell carcinoma of the skin</title><author>Stravodimou, Aristea ; Tzelepi, Vassiliki ; Papadaki, Helen ; Mouzaki, Athanasia ; Georgiou, Sophia ; Melachrinou, Maria ; Kourea, Eleni P.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3533-f99dc164ef8606d2658c13da0687257d4fc76f8e0deea0d86a615d2c768be35a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>actinic keratosis</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Carcinogenesis</topic><topic>Carcinoma in Situ - immunology</topic><topic>Carcinoma in Situ - pathology</topic><topic>Carcinoma, Squamous Cell - immunology</topic><topic>Carcinoma, Squamous Cell - pathology</topic><topic>CD3 antigen</topic><topic>CD4 antigen</topic><topic>CD8 antigen</topic><topic>Cytotoxicity</topic><topic>Female</topic><topic>Foxp3 protein</topic><topic>Humans</topic><topic>Image processing</topic><topic>in situ squamous cell carcinoma</topic><topic>invasive squamous cell carcinoma</topic><topic>Invasiveness</topic><topic>Keratosis</topic><topic>Keratosis, Actinic - immunology</topic><topic>Keratosis, Actinic - pathology</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Lymphocytes, Tumor-Infiltrating - immunology</topic><topic>Lymphocytes, Tumor-Infiltrating - pathology</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Paraffin</topic><topic>Precancerous Conditions - immunology</topic><topic>Precancerous Conditions - pathology</topic><topic>regulatory T‐cells (Tregs)</topic><topic>Retrospective Studies</topic><topic>Skin diseases</topic><topic>Skin Neoplasms - immunology</topic><topic>Skin Neoplasms - pathology</topic><topic>Squamous cell carcinoma</topic><topic>T-Lymphocyte Subsets - immunology</topic><topic>T-Lymphocyte Subsets - pathology</topic><topic>tumor infiltrating lymphocytes (TILs)</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Stravodimou, Aristea</creatorcontrib><creatorcontrib>Tzelepi, Vassiliki</creatorcontrib><creatorcontrib>Papadaki, Helen</creatorcontrib><creatorcontrib>Mouzaki, Athanasia</creatorcontrib><creatorcontrib>Georgiou, Sophia</creatorcontrib><creatorcontrib>Melachrinou, Maria</creatorcontrib><creatorcontrib>Kourea, Eleni P.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Journal of cutaneous pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Stravodimou, Aristea</au><au>Tzelepi, Vassiliki</au><au>Papadaki, Helen</au><au>Mouzaki, Athanasia</au><au>Georgiou, Sophia</au><au>Melachrinou, Maria</au><au>Kourea, Eleni P.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evaluation of T‐lymphocyte subpopulations in actinic keratosis, in situ and invasive squamous cell carcinoma of the skin</atitle><jtitle>Journal of cutaneous pathology</jtitle><addtitle>J Cutan Pathol</addtitle><date>2018-05</date><risdate>2018</risdate><volume>45</volume><issue>5</issue><spage>337</spage><epage>347</epage><pages>337-347</pages><issn>0303-6987</issn><eissn>1600-0560</eissn><abstract>Background
Tumor infiltrating lymphocytes (TILs) represent important regulators of carcinogenesis. Cutaneous invasive squamous cell carcinoma (inSCC) develops through precursor lesions, namely in situ squamous cell carcinoma (isSCC) and actinic keratosis (AK), representing a natural model of carcinogenesis. The study evaluates TIL subpopulations in inSCC and its precursors by comparing 2 semiquantitative scoring systems, and assesses the presence of regulatory T‐cells (Tregs) in these lesions.
Methods
Paraffin sections from 33 cases of AK, 19 isSCCs and 34 inSCCs with adjacent precursor lesions or normal skin (NS) were immunostained for CD3, CD4, CD8 and Foxp3. TIL subgroups were evaluated by the semiquantitative Klintrup‐Mäkinen (K‐M) score, and by a more detailed modification of this system. Treg counts were assessed by image analysis quantification.
Results
An increase of all TIL subpolulations from precursor lesions toward inSCC was shown by both scoring systems. Treg counts progressively increased from NS to AK and isSCC, but decreased in inSCC. Tregs were more numerous in pT2 and around indolent inSCCs compared to T1 and aggressive subtypes.
Conclusions
T‐cells and cytotoxic T‐cells progressively increase in cutaneous squamous cell carcinogenesis, while Treg counts diminish in inSCC. The K‐M score is an appropriate, easily applicable TIL scoring system in cutaneous inSCC.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>29419888</pmid><doi>10.1111/cup.13123</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0001-8838-8334</orcidid></addata></record> |
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subjects | actinic keratosis Aged Aged, 80 and over Carcinogenesis Carcinoma in Situ - immunology Carcinoma in Situ - pathology Carcinoma, Squamous Cell - immunology Carcinoma, Squamous Cell - pathology CD3 antigen CD4 antigen CD8 antigen Cytotoxicity Female Foxp3 protein Humans Image processing in situ squamous cell carcinoma invasive squamous cell carcinoma Invasiveness Keratosis Keratosis, Actinic - immunology Keratosis, Actinic - pathology Lymphocytes Lymphocytes T Lymphocytes, Tumor-Infiltrating - immunology Lymphocytes, Tumor-Infiltrating - pathology Male Middle Aged Paraffin Precancerous Conditions - immunology Precancerous Conditions - pathology regulatory T‐cells (Tregs) Retrospective Studies Skin diseases Skin Neoplasms - immunology Skin Neoplasms - pathology Squamous cell carcinoma T-Lymphocyte Subsets - immunology T-Lymphocyte Subsets - pathology tumor infiltrating lymphocytes (TILs) |
title | Evaluation of T‐lymphocyte subpopulations in actinic keratosis, in situ and invasive squamous cell carcinoma of the skin |
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