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Acute Radiation Colitis after Preoperative Short-Course Radiotherapy for Rectal Cancer: A Morphological, Immunohistochemical and Genetic Study

SIMPLE SUMMARY: Radiotherapy is the standard treatment for locally advanced rectal cancer with a high risk of local recurrence, if treated with surgery alone. The two regimens accepted are preoperative long-course radiotherapy with concomitant chemotherapy and preoperative short-course radiotherapy....

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Autores principales: Zanelli, Magda, Ciarrocchi, Alessia, De Petris, Giovanni, Zizzo, Maurizio, Costantini, Massimo, Bisagni, Alessandra, Torricelli, Federica, Nicoli, Davide, Ramundo, Dafne, Ricci, Stefano, Palicelli, Andrea, Sanguedolce, Francesca, Ascani, Stefano, Ruiz, Carolina Castro, Annessi, Valerio, Zamponi, Raffaella, Bortesi, Mara, Martino, Veronica, Marchetti, Marialisa, De Marco, Loredana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563849/
https://www.ncbi.nlm.nih.gov/pubmed/32917028
http://dx.doi.org/10.3390/cancers12092571
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author Zanelli, Magda
Ciarrocchi, Alessia
De Petris, Giovanni
Zizzo, Maurizio
Costantini, Massimo
Bisagni, Alessandra
Torricelli, Federica
Nicoli, Davide
Ramundo, Dafne
Ricci, Stefano
Palicelli, Andrea
Sanguedolce, Francesca
Ascani, Stefano
Ruiz, Carolina Castro
Annessi, Valerio
Zamponi, Raffaella
Bortesi, Mara
Martino, Veronica
Marchetti, Marialisa
De Marco, Loredana
author_facet Zanelli, Magda
Ciarrocchi, Alessia
De Petris, Giovanni
Zizzo, Maurizio
Costantini, Massimo
Bisagni, Alessandra
Torricelli, Federica
Nicoli, Davide
Ramundo, Dafne
Ricci, Stefano
Palicelli, Andrea
Sanguedolce, Francesca
Ascani, Stefano
Ruiz, Carolina Castro
Annessi, Valerio
Zamponi, Raffaella
Bortesi, Mara
Martino, Veronica
Marchetti, Marialisa
De Marco, Loredana
author_sort Zanelli, Magda
collection PubMed
description SIMPLE SUMMARY: Radiotherapy is the standard treatment for locally advanced rectal cancer with a high risk of local recurrence, if treated with surgery alone. The two regimens accepted are preoperative long-course radiotherapy with concomitant chemotherapy and preoperative short-course radiotherapy. The aim of our retrospective study is to provide a comprehensive morphological description of radiation-induced changes in rectal cancer specimens. We compared 2 groups of 95 rectal cancer patients treated preoperatively with either short-course (45 patients) or long-course radiotherapy (50 patients). Interestingly, in the non-neoplastic mucosa we identified features closely mimicking dysplasia/pre-neoplasia only in the group treated with short-course radiotherapy. Pathologists awareness of radiation-induced abnormalities is essential, as the misinterpretation may lead to patient’s overtreatment. In our study, next generation sequencing analysis supported the morphological concept that short-course radiotherapy-induced abnormalities do not represent true dysplasia, as somatic mutations were not identified in “dysplastic-like” tissues. ABSTRACT: Preoperative radiotherapy is a widely accepted treatment procedure in rectal cancer. Radiation-induced changes in the tumor are well described, whereas less attention has been given to the non-neoplastic mucosa. Our aim is to provide a detailed analysis of the morphological features present in non-neoplastic mucosa that pathologists need to be familiar with, in order to avoid misdiagnosis, when evaluating rectal cancer specimens of patients preoperatively treated with radiotherapy, especially with short-course regimen. We compared 2 groups of 95 rectal cancer patients treated preoperatively with either short-course (45 patients) or long-course radiotherapy (50 patients). Depending on the type of protocol, different histopathological features, in terms of inflammation, glandular abnormalities and endocrine differentiation were seen in the non-neoplastic mucosa within the irradiated volume. Of note, features mimicking dysplasia, such as crypt distortion, nuclear and cytoplasmic atypia of glandular epithelium, were identified only in the short-course group. DNA mutation analysis, using a panel of 56 genes frequently mutated in cancer, and p53 immunostaining were performed on both tumor and radiation-damaged mucosa in a subset of short course cases. Somatic mutations were identified only in tumors, supporting the concept that tissues with radiation-induced “dysplastic-like” features are not genetically transformed. Pathologists should be aware of the characteristic morphological changes induced by radiation. The presence of features simulating dysplasia in the group treated with short-course radiotherapy may lead to serious diagnostic mistakes, if erroneously interpreted. Next generation sequencing (NGS) analysis further validated the morphological concept that radiation-induced abnormalities do not represent pre-neoplastic lesions.
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spelling pubmed-75638492020-10-27 Acute Radiation Colitis after Preoperative Short-Course Radiotherapy for Rectal Cancer: A Morphological, Immunohistochemical and Genetic Study Zanelli, Magda Ciarrocchi, Alessia De Petris, Giovanni Zizzo, Maurizio Costantini, Massimo Bisagni, Alessandra Torricelli, Federica Nicoli, Davide Ramundo, Dafne Ricci, Stefano Palicelli, Andrea Sanguedolce, Francesca Ascani, Stefano Ruiz, Carolina Castro Annessi, Valerio Zamponi, Raffaella Bortesi, Mara Martino, Veronica Marchetti, Marialisa De Marco, Loredana Cancers (Basel) Article SIMPLE SUMMARY: Radiotherapy is the standard treatment for locally advanced rectal cancer with a high risk of local recurrence, if treated with surgery alone. The two regimens accepted are preoperative long-course radiotherapy with concomitant chemotherapy and preoperative short-course radiotherapy. The aim of our retrospective study is to provide a comprehensive morphological description of radiation-induced changes in rectal cancer specimens. We compared 2 groups of 95 rectal cancer patients treated preoperatively with either short-course (45 patients) or long-course radiotherapy (50 patients). Interestingly, in the non-neoplastic mucosa we identified features closely mimicking dysplasia/pre-neoplasia only in the group treated with short-course radiotherapy. Pathologists awareness of radiation-induced abnormalities is essential, as the misinterpretation may lead to patient’s overtreatment. In our study, next generation sequencing analysis supported the morphological concept that short-course radiotherapy-induced abnormalities do not represent true dysplasia, as somatic mutations were not identified in “dysplastic-like” tissues. ABSTRACT: Preoperative radiotherapy is a widely accepted treatment procedure in rectal cancer. Radiation-induced changes in the tumor are well described, whereas less attention has been given to the non-neoplastic mucosa. Our aim is to provide a detailed analysis of the morphological features present in non-neoplastic mucosa that pathologists need to be familiar with, in order to avoid misdiagnosis, when evaluating rectal cancer specimens of patients preoperatively treated with radiotherapy, especially with short-course regimen. We compared 2 groups of 95 rectal cancer patients treated preoperatively with either short-course (45 patients) or long-course radiotherapy (50 patients). Depending on the type of protocol, different histopathological features, in terms of inflammation, glandular abnormalities and endocrine differentiation were seen in the non-neoplastic mucosa within the irradiated volume. Of note, features mimicking dysplasia, such as crypt distortion, nuclear and cytoplasmic atypia of glandular epithelium, were identified only in the short-course group. DNA mutation analysis, using a panel of 56 genes frequently mutated in cancer, and p53 immunostaining were performed on both tumor and radiation-damaged mucosa in a subset of short course cases. Somatic mutations were identified only in tumors, supporting the concept that tissues with radiation-induced “dysplastic-like” features are not genetically transformed. Pathologists should be aware of the characteristic morphological changes induced by radiation. The presence of features simulating dysplasia in the group treated with short-course radiotherapy may lead to serious diagnostic mistakes, if erroneously interpreted. Next generation sequencing (NGS) analysis further validated the morphological concept that radiation-induced abnormalities do not represent pre-neoplastic lesions. MDPI 2020-09-09 /pmc/articles/PMC7563849/ /pubmed/32917028 http://dx.doi.org/10.3390/cancers12092571 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zanelli, Magda
Ciarrocchi, Alessia
De Petris, Giovanni
Zizzo, Maurizio
Costantini, Massimo
Bisagni, Alessandra
Torricelli, Federica
Nicoli, Davide
Ramundo, Dafne
Ricci, Stefano
Palicelli, Andrea
Sanguedolce, Francesca
Ascani, Stefano
Ruiz, Carolina Castro
Annessi, Valerio
Zamponi, Raffaella
Bortesi, Mara
Martino, Veronica
Marchetti, Marialisa
De Marco, Loredana
Acute Radiation Colitis after Preoperative Short-Course Radiotherapy for Rectal Cancer: A Morphological, Immunohistochemical and Genetic Study
title Acute Radiation Colitis after Preoperative Short-Course Radiotherapy for Rectal Cancer: A Morphological, Immunohistochemical and Genetic Study
title_full Acute Radiation Colitis after Preoperative Short-Course Radiotherapy for Rectal Cancer: A Morphological, Immunohistochemical and Genetic Study
title_fullStr Acute Radiation Colitis after Preoperative Short-Course Radiotherapy for Rectal Cancer: A Morphological, Immunohistochemical and Genetic Study
title_full_unstemmed Acute Radiation Colitis after Preoperative Short-Course Radiotherapy for Rectal Cancer: A Morphological, Immunohistochemical and Genetic Study
title_short Acute Radiation Colitis after Preoperative Short-Course Radiotherapy for Rectal Cancer: A Morphological, Immunohistochemical and Genetic Study
title_sort acute radiation colitis after preoperative short-course radiotherapy for rectal cancer: a morphological, immunohistochemical and genetic study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563849/
https://www.ncbi.nlm.nih.gov/pubmed/32917028
http://dx.doi.org/10.3390/cancers12092571
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