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Journal of Thoracic Oncology : Official... Oct 2020A grading system for pulmonary adenocarcinoma has not been established. The International Association for the Study of Lung Cancer pathology panel evaluated a set of...
INTRODUCTION
A grading system for pulmonary adenocarcinoma has not been established. The International Association for the Study of Lung Cancer pathology panel evaluated a set of histologic criteria associated with prognosis aimed at establishing a grading system for invasive pulmonary adenocarcinoma.
METHODS
A multi-institutional study involving multiple cohorts of invasive pulmonary adenocarcinomas was conducted. A cohort of 284 stage I pulmonary adenocarcinomas was used as a training set to identify histologic features associated with patient outcomes (recurrence-free survival [RFS] and overall survival [OS]). Receiver operating characteristic curve analysis was used to select the best model, which was validated (n = 212) and tested (n = 300, including stage I-III) in independent cohorts. Reproducibility of the model was assessed using kappa statistics.
RESULTS
The best model (area under the receiver operating characteristic curve [AUC] = 0.749 for RFS and 0.787 for OS) was composed of a combination of predominant plus high-grade histologic pattern with a cutoff of 20% for the latter. The model consists of the following: grade 1, lepidic predominant tumor; grade 2, acinar or papillary predominant tumor, both with no or less than 20% of high-grade patterns; and grade 3, any tumor with 20% or more of high-grade patterns (solid, micropapillary, or complex gland). Similar results were seen in the validation (AUC = 0.732 for RFS and 0.787 for OS) and test cohorts (AUC = 0.690 for RFS and 0.743 for OS), confirming the predictive value of the model. Interobserver reproducibility revealed good agreement (k = 0.617).
CONCLUSIONS
A grading system based on the predominant and high-grade patterns is practical and prognostic for invasive pulmonary adenocarcinoma.
Topics: Adenocarcinoma; Adenocarcinoma of Lung; Humans; Lung Neoplasms; Neoplasm Staging; Prognosis; Reproducibility of Results; Retrospective Studies
PubMed: 32562873
DOI: 10.1016/j.jtho.2020.06.001 -
Nature Communications Dec 2023The mechanism underlying the development of tumors, particularly at early stages, still remains mostly elusive. Here, we report whole-genome long and short read...
The mechanism underlying the development of tumors, particularly at early stages, still remains mostly elusive. Here, we report whole-genome long and short read sequencing analysis of 76 lung cancers, focusing on very early-stage lung adenocarcinomas such as adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma. The obtained data is further integrated with bulk and spatial transcriptomic data and epigenomic data. These analyses reveal key events in lung carcinogenesis. Minimal somatic mutations in pivotal driver mutations and essential proliferative factors are the only detectable somatic mutations in the very early-stage of AIS. These initial events are followed by copy number changes and global DNA hypomethylation. Particularly, drastic changes are initiated at the later AIS stage, i.e., in Noguchi type B tumors, wherein cancer cells are exposed to the surrounding microenvironment. This study sheds light on the pathogenesis of lung adenocarcinoma from integrated pathological and molecular viewpoints.
Topics: Humans; Adenocarcinoma of Lung; Lung Neoplasms; Adenocarcinoma; Lung; Adenocarcinoma in Situ; Mutation; Tumor Microenvironment
PubMed: 38102134
DOI: 10.1038/s41467-023-43732-y -
Journal of Thoracic Oncology : Official... May 2022The new grading system proposed by the Pathology Committee of the International Association for the Study of Lung Cancer in 2020 was based on the combination of the...
INTRODUCTION
The new grading system proposed by the Pathology Committee of the International Association for the Study of Lung Cancer in 2020 was based on the combination of the histologically predominant subtype and high-grade component. Because the predominant subtypes are associated with characteristic subsets, unique subsets can be identified by this grading system.
METHODS
We analyzed the clinicopathologic, genotypic, and prognostic features of a cohort of 781 consecutive patients with invasive nonmucinous adenocarcinoma of the lung.
RESULTS
Grade 3 tumors were associated with younger age, male sex, a higher smoking dose, and aggressive features (tumor size, lymph node metastasis, stage, lymphovascular invasion, and pleural invasion). Recurrence-free survival and 3-year overall survival were well-stratified according to tumor grade, and the differences were confirmed with multivariate analysis using the Cox proportional hazard model. Radiologically, most grade 3 tumors exhibit a solid nodular pattern on computed tomography images and a high maximum standardized uptake value with positron emission tomography. Genotypically, 43% of the grade 3 adenocarcinomas lacked any driver mutations, although one of the driver mutations was detected in 79% of grade 1 or 2 tumors. Patient age, positive smoking history, solid nodule on computed tomography image, and higher maximum standardized uptake value were identified as significant preoperative predictive factors of grade 3 tumors, with a prediction rate greater than 90%.
CONCLUSIONS
Besides stratifying the patient outcomes, the new grading system characterized unique clinicopathologic subsets and this study suggested that grade 3 tumors could be predicted using the preoperative variables.
Topics: Adenocarcinoma; Adenocarcinoma of Lung; Humans; Lung Neoplasms; Male; Neoplasm Staging; Prognosis; Retrospective Studies
PubMed: 35227909
DOI: 10.1016/j.jtho.2022.02.005 -
Histopathology Jan 2024Invasive mucinous adenocarcinoma (IMA) is a relatively rare subtype of lung adenocarcinoma, composed of goblet and/or columnar tumour cells containing abundant... (Review)
Review
Invasive mucinous adenocarcinoma (IMA) is a relatively rare subtype of lung adenocarcinoma, composed of goblet and/or columnar tumour cells containing abundant intracytoplasmic mucin vacuoles. While a majority of IMAs are driven by KRAS mutations, recent studies have identified distinct genomic alterations, such as NRG1 and ERBB2 fusions. IMAs also more frequently present as a pneumonic-like pattern with multifocal and multilobar involvement, and comparative genomic profiling predominantly shows a clonal relationship, suggesting intrapulmonary metastases rather than synchronous primary tumours. Accordingly, these unique features require different therapeutic approaches when compared to nonmucinous adenocarcinomas in general. In this article, we review recent updates on the histopathological, clinical, and molecular features of IMAs, and also highlight some unresolved issues for future studies.
Topics: Humans; Lung Neoplasms; Adenocarcinoma of Lung; Adenocarcinoma, Mucinous; Adenocarcinoma; Mutation
PubMed: 37867404
DOI: 10.1111/his.15064 -
Drug Resistance Updates : Reviews and... Nov 2023Adenocarcinoma is a common type of malignant tumor, originating from glandular epithelial cells in various organs, such as pancreas, breast, lung, stomach, colon,... (Review)
Review
Adenocarcinoma is a common type of malignant tumor, originating from glandular epithelial cells in various organs, such as pancreas, breast, lung, stomach, colon, rectus, and prostate. For patients who lose the opportunity for radical surgery, medication is available to provide potential clinical benefits. However, drug resistance is a big obstacle to obtain desired clinical prognosis. In this review, we provide a summary of treatment strategies and drug resistance mechanisms in adenocarcinoma of different organs, including pancreatic cancer, gastric adenocarcinoma, colorectal adenocarcinoma, lung adenocarcinoma, and prostate cancer. Although the underlying molecular mechanisms involved in drug resistance of adenocarcinoma vary from one organ to the other, there are several targets that are universal for drug resistance in adenocarcinoma, and targeting these molecules could potentially reverse drug resistance in the treatment of adenocarcinomas.
Topics: Male; Humans; Adenocarcinoma; Prostatic Neoplasms; Colorectal Neoplasms; Pancreatic Neoplasms
PubMed: 37678078
DOI: 10.1016/j.drup.2023.101002 -
Thoracic Surgery Clinics Nov 2022Esophageal cancer is the sixth most common cause of cancer mortality worldwide and is considered a major worldwide health challenge. Most patients diagnosed with... (Review)
Review
Esophageal cancer is the sixth most common cause of cancer mortality worldwide and is considered a major worldwide health challenge. Most patients diagnosed with esophageal cancer require extensive workup and management strategies. Multiple clinical trials have been conducted to evaluate the role of chemotherapy, chemoradiotherapy, and recently immunotherapy before or after surgery in the setting of localized esophageal cancer. Trimodality approaches, including preoperative chemoradiation followed by surgery or perioperative chemotherapy, have been widely accepted for treating localized esophageal cancer. However, the addition of immunotherapy to the current trimodality approach produced an advantage in disease-free survival. Our review will focus on the existing data on adjuvant therapies for locally advanced esophageal and gastroesophageal adenocarcinomas and squamous cell carcinomas.
Topics: Humans; Esophageal Neoplasms; Combined Modality Therapy; Adenocarcinoma; Chemoradiotherapy; Carcinoma, Squamous Cell; Chemoradiotherapy, Adjuvant; Neoadjuvant Therapy; Chemotherapy, Adjuvant
PubMed: 36266033
DOI: 10.1016/j.thorsurg.2022.06.004 -
Clinics in Laboratory Medicine Jun 2024Upper gastroesophageal carcinomas consist of cancers arising from the esophagus and stomach. Squamous cell carcinomas and adenocarcinomas are seen in the esophagus and... (Review)
Review
Upper gastroesophageal carcinomas consist of cancers arising from the esophagus and stomach. Squamous cell carcinomas and adenocarcinomas are seen in the esophagus and despite arising from the same organ have different biology. Gastric adenocarcinomas are categorized into 4 molecular subtypes: high Epstein-Barr virus load, microsatellite unstable cancers, chromosomal unstable (CIN) cancers, and genomically stable cancers. Genomically stable gastric cancers correlate highly with histologically defined diffuse-type cancers. Esophageal carcinomas and CIN gastric cancers often are driven by high-level amplifications of oncogenes and contain a high degree of intratumoral heterogeneity. Targeted therapeutics is an active area of research for gastroesophageal cancers.
Topics: Humans; Adenocarcinoma; Carcinoma, Squamous Cell; Esophageal Neoplasms; Stomach Neoplasms
PubMed: 38821643
DOI: 10.1016/j.cll.2023.08.005 -
Colorectal Disease : the Official... Jun 2023Perianal Paget's disease (PAPD) is a rare disorder with a predisposition to anal and colorectal malignancies and an unclear prognosis. Our previous 25-year series...
AIM
Perianal Paget's disease (PAPD) is a rare disorder with a predisposition to anal and colorectal malignancies and an unclear prognosis. Our previous 25-year series demonstrated a non-aggressive nature. This study aims to describe our updated institutional experience.
METHODS
This is a retrospective review of all patients diagnosed with primary PAPD from 1991 to 2021. A prospectively maintained institutional database was searched which included demographics, clinical and pathological manifestations, treatment methods, recurrence, oncological outcome and mortality.
RESULTS
Thirty patients were diagnosed with PAPD. Fifteen were women (50%); the average age at diagnosis was 71 ± 10.7 years, and the average lesion size was 3.7 ± 2.6 cm. At diagnosis, 12 (40%) were harbouring invasive anal adenocarcinoma. Eight (27%) developed adenocarcinomas concurrent with PAPD recurrence at a mean interval of 9 ± 4.4 years (range 1.9-14.8). The Kaplan-Meier curve estimated overall survival of 93%, 86%, 82%, 65% and 56% at 1, 3, 5, 10 and 15 years, respectively. Median survival was 16 years. Six (20%) had disease-related mortality. Initially, nine (30%) were treated with abdominoperineal resection (APR), 15 (50%) underwent local resection, three (10%) were treated with radiotherapy, two (7%) received only topical therapy and one (3%) chose observation. Fifteen (50%) experienced recurrence of PAPD, two after undergoing APR. Five (17%) had persistent disease until death. Only 10 (33%) did not experience PAPD recurrence, seven of whom underwent APR. The mean follow-up time was 9.2 ± 6.2 years.
CONCLUSIONS
Perianal Paget's disease is an aggressive entity with high rates of synchronous anal adenocarcinoma at diagnosis and development of metachronous adenocarcinoma later in life.
Topics: Humans; Female; Male; Paget Disease, Extramammary; Adenocarcinoma; Anus Neoplasms; Prognosis; Anal Canal
PubMed: 36945125
DOI: 10.1111/codi.16549 -
Asian Pacific Journal of Cancer... Feb 2023Today, genomic changes are an important cause of the occurrence, growth and progression of cancer. Technological advances in cancer genomic analysis platforms have made...
BACKGROUND
Today, genomic changes are an important cause of the occurrence, growth and progression of cancer. Technological advances in cancer genomic analysis platforms have made it possible to identify genomic alterations that may influence response to lung cancer treatment.
METHODS
The study examined tumor growth-inhibiting oncogenes and genes responsible for cell growth and division to identify mutations characteristic of malignant lung tumors. The mutations were studied in 400 postoperative samples after amplifying p53 and HRAS fragments and p53, p21Waf1, MDM2 mRNA. p53 or p21Waf1 were expressed in 50% of squamous cell carcinomas and adenocarcinomas of the lung.
RESULTS
The study examined tumor growth-inhibiting oncogenes and genes responsible for cell growth and division to identify mutations characteristic of malignant lung tumors. The mutations were studied in 400 postoperative samples after amplifying p53 and HRAS fragments and p53, p21Waf1, MDM2 mRNA. p53 or p21Waf1 were expressed in 50% of squamous cell carcinomas and adenocarcinomas of the lung. HRAS mutations were present in most squamous cell carcinomas and adenocarcinomas of the lung. EcoR1- and Pst1- restriction enzymes destroyed the RT-PCR product of the p53 and p21Waf1 mRNA and increased the level of detected mutations in lung adenocarcinoma to 75% and 50 %, respectively. EGFR mutations were more frequent in lung adenocarcinoma than in lung squamous cell carcinoma. Mutations in EGFR exons 19 and 21 found in 65 of 263 lung tumor samples indicated the tumor sensitivity to EGFR tyrosine kinase inhibitors. EGFR deletions in exon 19 occurred mainly in adenocarcinoma, L858R mutations in EGFR exon 21 were quite common in lung adenocarcinoma.
CONCLUSION
The mutations detected in most squamous cell carcinomas and adenocarcinomas of the lung could be used to diagnose and predict the disease severity and targeted therapy efficacy.
Topics: Humans; Tumor Suppressor Protein p53; Lung Neoplasms; Mutation; Adenocarcinoma of Lung; Adenocarcinoma; Carcinoma, Squamous Cell; ErbB Receptors
PubMed: 36853323
DOI: 10.31557/APJCP.2023.24.2.709 -
Bulletin Du Cancer May 2023Gastric cancer is the 6th most common cancer in the world. Gastric adenocarcinomas can be divided into two groups: gastroesophageal junction adenocarcinomas and distal... (Review)
Review
Gastric cancer is the 6th most common cancer in the world. Gastric adenocarcinomas can be divided into two groups: gastroesophageal junction adenocarcinomas and distal gastric adenocarcinomas, with different risk factors and potentially different therapeutic strategies. Therapeutic strategy for esogastric adenocarcinoma is multimodal. Gastric adenocarcinomas are managed with surgery and peri-operative chemotherapy. Gastroesophageal junction adenocarcinomas can either be treated surgically after neoadjuvant chemoradiotherapy or in the same way than gastric adenocarcinomas. There is currently no evidence of superiority of either treatment strategy. Recently, nivolumab has been validated as an adjuvant therapy for patients with esophageal cancer who received preoperative chemoradiotherapy and had residual tumor on the surgical specimen. In the absence of preoperative treatment, adjuvant chemoradiotherapy or chemotherapy should be discussed on a patient-by-patient basis. Currently, there is not indication for targeted therapies, nor for adapting postoperative treatment according to the response to preoperative treatment. The only validated indication for immunotherapy is as adjuvant treatment of esophageal cancer, but many studies are ongoing and may change practices in the future. The objective of this review is to synthesize the literature concerning the management of localized esogastric adenocarcinoma.
Topics: Humans; Combined Modality Therapy; Stomach Neoplasms; Chemoradiotherapy, Adjuvant; Neoadjuvant Therapy; Esophageal Neoplasms; Adenocarcinoma; Esophagogastric Junction; Antineoplastic Combined Chemotherapy Protocols
PubMed: 35965103
DOI: 10.1016/j.bulcan.2022.05.014