Pulmonary Metastases Of Colorectal Cancer Research Articles

METTL3 recruiting M2-type immunosuppressed macrophages by targeting m6A-SNAIL-CXCL2 axis to promote colorectal cancer pulmonary metastasis

BackgroundThe regulatory role of N6-methyladenosine (m6A) modification in the onset and progression of cancer has garnered increasing attention in recent years. However, the specific role of m6A modification in pulmonary metastasis of colorectal cancer remains unclear.MethodsThis study identified differential m6A gene expression between primary colorectal cancer and its pulmonary metastases using transcriptome sequencing and immunohistochemistry. We investigated the biological function of METTL3 gene both in vitro and in vivo using assays such as CCK-8, colony formation, wound healing, EDU, transwell, and apoptosis, along with a BALB/c nude mouse model. The regulatory mechanisms of METTL3 in colorectal cancer pulmonary metastasis were studied using methods like methylated RNA immunoprecipitation quantitative reverse transcription PCR, RNA stability analysis, luciferase reporter gene assay, Enzyme-Linked Immunosorbent Assay, and quantitative reverse transcription PCR.ResultsThe study revealed high expression of METTL3 and YTHDF1 in the tumors of patients with pulmonary metastasis of colorectal cancer. METTL3 promotes epithelial-mesenchymal transition in colorectal cancer by m6A modification of SNAIL mRNA, where SNAIL enhances the secretion of CXCL2 through the NF-κB pathway. Additionally, colorectal cancer cells expressing METTL3 recruit M2-type macrophages by secreting CXCL2.ConclusionMETTL3 facilitates pulmonary metastasis of colorectal cancer by targeting the m6A-Snail-CXCL2 axis to recruit M2-type immunosuppressive macrophages. This finding offers new research directions and potential therapeutic targets for colorectal cancer treatment.

Primary tumor resection improves prognosis of unresectable carcinomas of the transverse colon including flexures with pulmonary metastasis: a cohort study.

Studies of unresectable colorectal cancer pulmonary metastasis (CRPM) have rarely analyzed patient prognosis from the perspective of colonic subsites. This study aimed to evaluate the effects of primary tumor resection (PTR) on the prognosis of patients with unresectable pulmonary metastases of transverse colon cancer pulmonary metastasis (UTCPM), hepatic flexure cancer pulmonary metastasis (UHFPM), and splenic flexure cancer pulmonary metastasis (USFPM). Patients were identified from the Surveillance, Epidemiology, and End Results database between 2000 and 2018. The Cox proportional hazards regression models were used to identify prognostic factors of overall survival (OS) and cause-specific survival (CSS). The Kaplan-Meier analyses and log-rank tests were conducted to assess the effectiveness of PTR on survival. This study included 1294 patients: 419 with UHFPM, 636 with UTCPM, and 239 with USFPM. Survival analysis for OS and CSS in the PTR groups, showed that there were no statistical differences in the the UHFPM, UTCPM, and USFPM patients. There were statistical differences in the UHFPM, UTCPM, and USFPM patients for OS and CSS. Three non-PTR subgroups showed significant statistical differences for OS and CSS. We confirmed the different survival rates of patients with UTCPM, UHFPM, and USFPM and proved for the first time that PTR could provide survival benefits for patients with unresectable CRPM from the perspective of the colonic subsites of the transverse colon, hepatic flexure, and splenic flexure.

Tertiary lymphoid structures in pulmonary metastases of microsatellite stable colorectal cancer

Tertiary lymphoid structures (TLSs) are ectopic lymphoid aggregates located at sites of chronic inflammation and recognized as prognosticators in several cancers. We aimed to analyse the prognostic effect of TLSs in colorectal cancer (CRC) pulmonary metastases and primary tumours, with a comparison to the CD3+ and CD8+ cell density-based immune cell score (ICS). For TLS density and TLS maximum diameter analysis, 67 pulmonary metastases and 63 primary tumours were stained with haematoxylin and eosin. For ICS scoring and analysis, CD3 and CD8 immunohistochemistry was performed. Excellent interobserver agreement was achieved in all TLS measurements. Of all patients, 36 patients had low TLS density (< 0.222 follicles/mm) and 31 patients had high TLS density (≥ 0.222 follicles/mm) in the first resected pulmonary metastases. TLS density (adjusted HR 0.91, 0.48–1.73) or maximum diameter (adjusted HR 0.78, 0.40–1.51) did not have prognostic value in pulmonary metastases. In primary tumours, higher TLS density (adjusted HR 0.39, 0.18–0.87) and maximum diameter (adjusted HR 0.28, 0.11–0.73) were associated with lower mortality. In the pulmonary metastases, ICS had superior prognostic value to TLSs; however, TLSs and ICS were significantly associated. In conclusion, TLSs in CRC pulmonary metastases had no prognostic value but correlated with the ICS. TLSs in primary tumours associated with favourable prognosis.

Microwave Ablation for Pulmonary Metastases: A Systematic Review

Radiofrequency ablation (RFA) for colorectal cancer pulmonary metastases (CRCPulM) has been studied since 2000 and shown to be safe. Recently, microwave ablation (MWA) has grown in popularity for CRCPulM. However, short- to long-term efficacy of MWA has yet to be understood.

PO-1402 SBRT for pulmonary metastasis of colorectal cancer: biologically effective dose 150 Gy is preferred

PO-1402 SBRT for pulmonary metastasis of colorectal cancer: biologically effective dose 150 Gy is preferred

Exploring the Pathogenesis of Pulmonary Metastasis of Colorectal Cancer based on “the Lung and the Large Intestine are in Close Proximity”

Exploring the Pathogenesis of Pulmonary Metastasis of Colorectal Cancer based on “the Lung and the Large Intestine are in Close Proximity”

Comparison of Microwave and Radiofrequency Ablation in the Treatment of Pulmonary Metastasis of Colorectal Cancer.

Radiofrequency ablation (RFA) for colorectal cancer pulmonary metastases (CRCPulM) has been shown to be safe. Microwave ablation (MWA) has emerged in the treatment for CRCPulM. However, short to long-term efficacy of both modalities have yet to be understood. This is a retrospective study of 203 patients who received RFA and MWA from 2000-2018 at a major tertiary hospital in Australia. A total of 161 patients underwent RFA and 42 MWA. Median ablation size and time was 4 (range=3-5 cm) vs. 3.5 cm (range=3-4 cm; p=0.0395) and 49 (range=26-65 min) vs. 8 min (5-13 min) in the RFA and MWA groups, respectively (p<0.001). The complication rate was 112 (55%) and 40 (74%) in the RFA and MWA group, respectively (p=0.011). Life-threatening pulmonary haemorrhage occurred in 1 (0.5%) and 4 (7.4%) patients in the RFA and MWA group, respectively (p=0.007). Local recurrences detected after discharge were similar in both groups [28% (p<0.001)]. However, the MWA group demonstrated higher survival rate and less recurrence rate than RFA in the first 24 months of follow up. RFA and MWA are competitive treatment methods for CRCPulM. Although MWA has significantly higher complication rate than RFA, it can be performed in a much shorter time and lead to a shorter length of hospital stay.

Genetic Characteristics of Resectable Colorectal Cancer with Pulmonary Metastasis.

The lung is the most common extra-abdominal metastasis site of colorectal cancer (CRC). This study aimed to investigate the genetic variation of pulmonary metastases (PM) and primary tumors in resectable CRC. The clinical data of 410 patients with PM after CRC surgery and 33 paraffin-embedded tissue samples from January 2012 to July 2019 in our hospital were collected retrospectively. Next, 450-panel gene detection technologies based on next-generation sequencing (NGS) were used to analyze the changes in the gene map and the overall variation in cancer-related genes in PM and primary tumors. After quality control, 19 samples were included in the final gene analysis. The results showed that APC (89.5%), TP53 (89.5%), and KRAS (53%) were the most common mutations in PM and primary tumors, but the gene amplification variation was enriched in primary tumors (4.6% vs. 11.4%). KRAS G12D was the most common site variation of the KRAS gene in both PM and primary tumors of CRC. There was no hotspot mutation in the TP53 locus in CRC, and the TP53 mutation in the PM was consistent with that in the primary lesion. The microsatellite instability (MSI) levels of 10 patients were MSS. The mean tumor mutation burden (TMB) of the primary tumor (5.3 muts·Mb−1) was slightly higher than that of metastasis (5.0 muts·Mb−1). In our institution, the genetic characteristics of resectable PM from CRC may be highly consistent with those of the primary tumor.

Prognostic Factors in Stage IV Colorectal Cancer Patients With Resection of Liver and/or Pulmonary Metastases: A Population-Based Cohort Study

ImportanceCurrently, surgical resection of distant metastatic lesions has become the preferred treatment for select colorectal cancer (CRC) patients with liver metastasis (LM) and/or pulmonary metastasis (PM). Metastasectomy is the most common curative method. However, evidence of the factors affecting the prognosis of CRC patients after resection of LM and/or PM is still insufficient.ObjectiveTo explore the prognostic factors of CRC patients with LM and/or PM who have undergone resection of metastatic tumors and to provide reliable selection factors for surgical treatment in patients affected by LM and/or PM from CRC.MethodsThe SEER database was used to identify eligible CRC LM and/or PM patients who underwent resection of the primary tumor and distant metastases from January 1, 2010, to December 31, 2018. The Kaplan–Meier method was used to calculate survival, and comparisons were performed using the log-rank test for univariate analysis. A Cox proportional hazards regression model was used to identify prognostic factors for the multivariate analysis. The outcomes included overall survival (OS) and cancer-specific survival (CSS).ResultsA total of 3,003 eligible colorectal cancer patients with LM and/or PM were included in this study. The 3-year and 5-year OS rates were 53% and 33.6%, respectively, and the 3-year and 5-year CSS rates were 54.2% and 35.3%, respectively. In the adjusted multivariate analysis, age < 65 years (OS: p=0.002, CSS: p=0.002) was associated with better long-term outcomes, and primary tumors located on the left side of the colon (OS: p=0.004, CSS: p=0.006) or rectum (OS: p=0.004, CSS: p=0.006), T3 stage (OS: p<0.001, CSS: p<0.001), number of regional lymph nodes examined ≥ 12 (OS: p<0.001, CSS: p=0.001), and CRC LM (OS: p<0.001, CSS: p<0.001) were positive prognostic factors for survival after resection of metastatic tumors.ConclusionAge < 65 years is associated with better long-term outcomes in colorectal cancer patients with LM and/or PM, analogously to the left sided primary tumor, T3 stage, number of regional lymph nodes examined ≥ 12 and liver metastases.

Abstract 2828: The prognostically significant immunological indices for patients who underwent curative resection of pulmonary metastases of colorectal cancer

Abstract Background: In recent years, it has been revealed that the immunological state of the host affects with the effect of cancer treatments. The neutrophil-to-lymphocyte ratio (NLR) as a systemic inflammatory marker and the density of tumor-infiltrating lymphocytes (TILs) at cancer microenvironment have been reported to be useful prognostic indices in various cancers, including colorectal cancer (CRC). The aim of this study is to evaluate the prognostic significance of immunological indices in patients who underwent curative resection of pulmonary metastases of CRC. Patients and Methods: The medical records of 17 patients who underwent potentially curative resection for pulmonary metastases of CRC were retrospectively reviewed. The correlation between the relapse-free survival (RFS) or the overall survival (OS) after curative resection of pulmonary metastases of CRC and the clinicopathological factors, NLR or TILs were evaluated. The NLR was calculated from the blood sample which was obtained within 2 weeks before pulmonary resection by dividing the absolute neutrophil count by the absolute lymphocyte count. According to the receiver operating characteristic (ROC) curve analysis, patients with an NLR of ≥ 2.5 were classified as high-NLR group. The density of TILs was examined by immunohistochemistry of pulmonary metastatic tumor sample, by staining anti-CD3 and anti-CD8 antibody. The number of CD3+TILs and CD8+TILs at the border of tumor was counted in a randomly selected field at a magnification of ×400. The mean of the values obtained in five different areas was used. According to the ROC curve analysis, the patients with the number of CD3+TILs ≥ 31 were classified as high- CD3+TILs group and patients with the number of CD8+TILs ≥ 21 were classified as high- CD8+TILs group. Results: The RFS and OS after resection of pulmonary metastases were significantly worse in the high-NLR group than in the low-NLR group (p=0.001, p=0.003, respectively). The RFS after resection of pulmonary metastases was significantly better in the high-CD3+TILs group than in the low-CD3+TILs group (p=0.041). Multivariate analysis revealed that the number of pulmonary metastases and the NLR before resection of pulmonary metastases were independent prognostic factors of the RFS (p=0.007, p=0.002, respectively) and the NLR before resection of pulmonary metastasis was the independent prognostic factor of the OS (p=0.009). Conclusion: The immunological indices such as the NLR and the density of TILs, may have prognostic significance in patients who underwent curative resection of pulmonary metastases of CRC. Citation Format: Yuki Okazaki, Masatsune Shibutani, En Wang, Hisashi Nagahara, Tatsunari Fukuoka, Yasuhito Iseki, Shinichiro Kashiwagi, Hiroaki Tanaka, Kiyoshi Maeda, Kosei Hirakawa, Masaichi Ohira. The prognostically significant immunological indices for patients who underwent curative resection of pulmonary metastases of colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2828.

Role of surgical resection and its alternative local therapy for pulmonary metastasis of colorectal cancer.

We reviewed surgical and alternative treatments for pulmonary metastasis of colorectal cancer, focusing on recent reports. The standard treatment for pulmonary metastasis of colorectal cancer is pulmonary resection, if resectable, despite the fact that the metastasis is hematogenous to distant organs. Guidelines in several countries, including Japan, have described pulmonary resection as a useful option because of the favorable long‐term prognosis reported in various studies pertaining to pulmonary resection. The indications for pulmonary resection have been reviewed in several studies; additionally, the number of metastases, pretreatment carcinoembryonic antigen value, and disease‐free interval from the primary resection to pulmonary recurrence have been proposed. However, no consensus has been reached to date. Contrastingly, recent advances in chemotherapy have remarkably improved the outcome of distant metastases, indicating that it is time to reconsider the significance of local treatment, including pulmonary resection. In addition to surgical resection, minimally invasive therapies, such as stereotactic body radiation therapy and radiofrequency ablation have been developed as local treatments for pulmonary metastases, and their long‐term results have been reported. Prospective controlled trials and large‐scale data analyses are needed to determine the best local treatment for pulmonary metastases and to find the appropriate indication for each treatment.

Prognostic Significance of the Immunological Indices in Patients Who Underwent Complete Resection of Pulmonary Metastases of Colorectal Cancer.

The neutrophil-to-lymphocyte ratio (NLR) and the density of tumor-infiltrating lymphocytes (TILs) have been reported as immunological prognostic factors for various cancers. We evaluated the association between the prognosis and the immunological status in patients who underwent complete resection of pulmonary metastases of colorectal cancer (CRC). We evaluated the associations between the NLR before the resection of pulmonary metastases and the relapse-free survival (RFS) or overall survival (OS), or between the density of TILs in the pulmonary metastasis and the RFS or OS. The RFS and OS were significantly worse in the NLR-High group than in the NLR-Low group. The RFS was significantly longer in the CD3+TILs-High group than in the CD3+TILs-Low group. The NLR and the density of TILs may have prognostic significance in patients who undergo complete resection of pulmonary metastases of CRC.

The Impact of Smoking on Pulmonary Metastasis in Colorectal Cancer.

IntroductionRecently, clinical studies have revealed that smoking can contribute to the poor prognosis of colorectal cancer (CRC) and, additionally, can be a risk factor for pulmonary metastasis of CRC. However, there has been no basic research regarding the underlying molecular mechanism. The purpose of this study was to clarify the mechanism by which smoking causes pulmonary metastasis of CRC.MethodsFirst, pulmonary metastasis model mice inhaled cigarette smoke or air (control) for 1 h once a day for 3 weeks. We attempted to clarify the effect of smoking on the incidence of pulmonary metastasis. On the 15th day, CMT-93 cells were injected into the tail vein. At 6 and 8 weeks following injection, the extent of pulmonary metastasis was evaluated using in vivo micro CT. After the last CT examination, the mice were sacrificed, and the lungs were extracted for pathological examination.ResultsThe number of mice with pulmonary metastases in the smoking group was significantly higher than in the control group. Three weeks of smoking induced mild inflammation in the lungs, as evidenced by increases in the levels of IL-6 and TNF-α in bronchoalveolar lavage. Moreover, the adhesion-related molecule ICAM-1 was overexpressed in pulmonary tissue, which allowed drained cancer cells to remain in the lung and contribute to the formation of pulmonary metastasis.ConclusionCollectively, cigarette smoking may contribute to the pathogenesis and development of pulmonary metastasis in CRC through enhancement of adhesion and inflammation.

What is the appropriate surgical strategy for pulmonary metastasis of colorectal cancer?

Pulmonary metastasectomy is considered to be a feasible method for selected colorectal cancer (CRC) patients. This study aimed to optimize the individualized surgical strategy of pulmonary metastasectomy, especially in choice of surgery extent and systematic mediastinal lymph nodes dissection.Data of 267 CRC patients who underwent pulmonary metastasectomy from July 2011 to July 2017 in Shanghai Cancer Center Fudan University were reviewed. Recurrence-free survival (RFS), overall survival (OS) and other clinical characteristics were compared between patients who accepted different surgical strategy.A total of 93 (34.8%) patients underwent lobectomy, 162 (60.7%) wedge resection, and 12 (4.5%) segmentectomy. Mediastinal lymph nodes dissection or sampling was performed in 106 (39.7%) patients. The median follow-up phase was 32.5 months (range 7.2–104.7 months). Patients were divided into 2 groups according to the surgical extent, lobectomy group and sublobar resection group. The median RFS and OS were 46.4 and 76.5 months for patients underwent, respectively. In the patients whose tumor diameter was ≥ 1.5 cm, RFS (5-year; 44.9% vs 29.8%, log-rank P = .03; hazard ratio, 0.71; 95% CI 0.52–0.89, P = .026) was better in the lobectomy group; however, no difference was found in OS. Meanwhile, in the patients whose tumor size was <1.5 cm, no difference was observed in RFS, as well as in OS. In the patients with metastatic lesion size ≥1.5 cm, a trend towards better RFS was found in patients received lymph nodes dissection, but it did not reach statistical significance.Lobectomy has more curative significance for CRC patients with single pulmonary metastatic lesion ≥1.5 cm. Systematic mediastinal lymph nodes dissection did not improve clinical outcome for CRC patients occurred pulmonary metastasis.

Phase II trial of adjuvant mFOLFOX6 after metastasectomy for pulmonary metastasis of colorectal cancer: WJOG5810G.

4097 Background: Resection of pulmonary metastasis (PM) is widely accepted to improve the prognosis in selected patients (pts) with metastatic colorectal cancer (CRC). However, the clinical implication of adjuvant chemotherapy after metastasectomy of PM is unknown. We conducted a multi-center phase 2 trial of adjuvant chemotherapy with mFOLFOX6 after metastasectomy of PM-CRC. Methods: Main eligibility criteria were first curative metastasectomy of 4 or less PMs and no prior chemotherapy except for adjuvant chemotherapy with fluoropyrimidine monotherapy after curative resection of primary or extrathoracic CRC metastasis. The study treatment was 12 courses of mFOLFOX6 (oxaliplatin 85 mg/m2, l-leucovorin 200 mg/m2, 5-fluorouracil 400 mg/m2 bolus followed by 2400 mg/m2 continuous infusion, every 2 w). The primary endpoint was overall survival (OS). The secondary endpoints included disease-free survival (DFS), adverse events (AEs), and recurrence sites. The sample size was determined to be 93 expecting 5-year OS rate of 50% with threshold 35% (90% power, alpha error 5%). Results: Fifty-two pts from 34 institutions were enrolled between July 2011 and July 2014. Patient enrollment was closed prematurely because of slow accrual. Four patients were ineligible after enrollment and the safety and efficacy cohort comprised 52 and 48 patients, respectively. Patient backgrounds were as follows: gender (male/female) 31/21, median age (range) 63 (42-75) years, ECOG PS (0/1) 48/4, primary site (colon/rectum) 18/34, number of PM (1/2/3/4) 36/9/5/2, synchronous/metachronous PM 11/41, and unilateral/bilateral PM 40/12. With the median follow-up time of 6.0 (1.8-7.7) years, 5-year OS rate was 86% (95% CI: 72-93) and 5-year DFS rate was 59% (95% CI: 43-71). Tumors recurred in 19 patients (13 lung, 3 liver and 7 others). Total 41 pts (79%) completed 12 courses of mFOLFOX6 (reasons for discontinuation: AEs in 3, refusal due to AEs in 8). AEs ( &gt; Grade 3) were neutropenia 50%, fatigue 8%, peripheral sensory neuropathy 8%, appetite loss 4%, diarrhea 4%, febrile neutropenia 2% and allergic reaction 2%. There was no treatment related death. Conclusions: Adjuvant mFOLFOX6 is feasible and may be effective after metastasectomy for PM-CRC, considering much better OS than we had expected. Clinical trial information: UMIN000005693 .

03:18 PM Abstract No. 280 Is microwave ablation superior to radiofrequency ablation in the treatment for pulmonary metastasis of colorectal cancer? One center’s 17-year experience in Australia

03:18 PM Abstract No. 280 Is microwave ablation superior to radiofrequency ablation in the treatment for pulmonary metastasis of colorectal cancer? One center’s 17-year experience in Australia

Long-Term Outcomes after Surgical Resection for Synchronous or Metachronous Hepatic and Pulmonary Colorectal Cancer Metastases

Background/Aims: At present, benefits of surgical resection and appropriate selection criteria in patients affected by both hepatic and pulmonary metastases of colorectal cancer (CRC) are under discussion. Our analysis focused on a surgical series of such patients and our final aim consisted in identifying potential prognostic factors. Methods: Eighty-five patients undergoing resection of both hepatic and pulmonary metastases at 2 Healthcare Institutions from January 1993 to June 2015 were retrospectively reviewed as concerned clinical information, surgical notes and pathological features. Patient, treatment, and outcome variables were analyzed by use of log-rank tests, Cox regression, and Kaplan-Meier methods. Results: Liver turned out as the first site of metastasis in 75% patients, lung in 13% patients, and both sites in 12% patients. Multiple hepatic metastases were detected in 67% patients and pulmonary metastases in 31% patients. Two hundred eighteen surgical interventions were performed (mean 2.56 for each patient). Overall survival (OS) rates at 3-, 5-, and 10-year follow-up from colorectal resection were 94, 79, and 38% respectively. Median OS was 8.31 years. Survival turned out significantly longer for patients with disease-free interval (DFI) exceeding 1 year between first metastasectomy and diagnosis of second metastases and in patients affected by metachronous pulmonary metastases. Conclusions: Surgical resection of both hepatic and pulmonary metastases of CRC represents a safe and effective treatment. It might lead to rewarding long-term survival rates in high selected patients. Shorter DFIs between first metastasectomy and diagnosis of second metastases can determine worse prognoses. In addition, poor outcomes could be predicted also for patients affected by synchronously detected pulmonary CRC metastases, although further confirmatory analyses are strongly required.

Ouctomes after metastasectomies compared with hepatic metastasis alone and hepatic and pulmonary metastasis with colorectal cancer

Background: Surgical resection for hepatic metastasis of colorectal cancer is an established procedures. However, the role of surgical resections in patients with both hepatic and pulmonary metastases in not well established. We aimed overall survival of patients with hepatic and pulmonary metastasis of colorectal cancer compared with hepatic metastasis alone.

Mutational profile of colorectal cancer lung metastases and paired primary tumors by targeted next generation sequencing: implications on clinical outcome after surgery.

Pulmonary metastasectomy is one of the cornerstones in the treatment of oligometastatic colorectal cancer (CRC). However, the selection of patients who benefit from a surgical resection is difficult. Mutational profiling has become an essential part of diagnosis and treatment of malignant disease. Despite this, comprehensive data on the mutational profile of CRC and its clinical impact in the context of pulmonary metastasectomy is sparse. We therefore aimed to provide a complete mutational status of CRC pulmonary metastases (PM) and corresponding primary tumors by targeted next-generation sequencing (tNGS), and correlate sequencing data with clinical outcome variables. Case-matched, formalin-fixed paraffin embedded surgical specimens of lung metastases (n=47) and matched primary CRC (n=24) were sequenced using the TruSeq Amplicon Cancer Panel (Illumina platform). Penalized Cox regression models were applied to identify mutations with prognostic impact. Mutations were found most frequently in APC, TP53 and KRAS, in both PM and matched primary tumors. Concordance between primary tumors and PM was 83.5%. Adaptive elastic-net regularized Cox regression models identified mutations being prognostic for time to pulmonary recurrence (EGFR, GNAQ, KIT, MET, and PTPN11) and for overall survival (OS) (PDGFRA, SMARCB1, and TP53). Our findings suggest that CRC PM harbor a variety of conserved and de novo mutations. We could identify a mutational profile predicting clinical outcome after pulmonary metastasectomy. Moreover, our data provide a rationale for future targeted therapies of patients with CRC lung metastases.

Immunohistochemical profiles in primary lung cancers and epithelial pulmonary metastases

Correct diagnosis of pulmonary tumors is essential for treatment decision and often relies on immunohistochemical markers. We stained tissue microarrays from resected primary lung cancer (n = 665) and pulmonary metastases (n = 425) for CK7, CK20, CDX2, CK5, p40, p63, TTF-1, napsin A, GATA3, and PAX8 to systematically assess the diagnostic value of these markers. Primary lung adenocarcinomas expressed TTF-1 in 90% and napsin A in 84% of the cases, whereas 10% were positive for p63, 7% for CDX2, 2% for CK20, and 2% for GATA3. Only 68% of the lung adenocarcinomas were positive for CK7, TTF-1, and napsin A and negative for all other markers. Primary lung squamous cell carcinomas expressed CK5, p40, and p63 in 94%-97% of cases, whereas 44% were positive for CK7, 20% for GATA3, 7% for CDX2, and 3% for TTF-1. Rare cases expressed PAX8, CK20, or napsin A. Pulmonary metastases of colorectal cancer were positive for CK20 in 83% and CDX2 in 99% of the cases. Rare cases expressed CK7, p63, or PAX8, whereas 4% expressed TTF-1. Pulmonary metastases of renal cell carcinomas were positive for PAX8 in 74%, napsin A in 7%, and CK7 in 7% of the cases. Pulmonary metastases of breast cancer were positive for GATA3 in 93% and CK7 in 78% of the cases, whereas 15% expressed CK5. Information on expression and patterns of immunohistochemical markers facilitates histopathological diagnostics. Evidently, unusual immune profiles occur and may lead to incorrect diagnosis.