Prognostic effect of stromal myofibroblasts in lung adenocarcinoma

Myofibroblasts are special cells with the features of both fibroblasts and smooth muscle cells, which are one of the most important cells in tumor stroma. The role of myofibroblasts in tumor stroma remains disputable. Some authors suggested that myofibroblasts can facilitate tumor progress, and another considered that myofibroblasts could prevent tumor cells diffusing. Bronchioloalveolar carcinoma (BAC) is a?kind of adenocarcinoma in situ. With the destruction of the alveolar framework by tumor growth, BAC develops into mixed BAC and invasive adenocarcinoma, which is a?natural model of transformation from carcinoma in situ to invasive carcinoma. In this study, the expression of myofibroblasts in BAC, mix-BAC and invasive adenocarcinoma was examined by immunohistochemical staining of surgical specimens from 102 patients. The results showed that positive expression of myofibroblasts in pure BAC (2/15, 13.33%) group was lower than in mix-BAC (17/38, 44.74%) and invasive adenocarcinoma (29/49, 59.18%) respectively, (p<0.05, p<0.01). In addition, myofibroblast positive expression was associated with lymph node metastasis, high stage, high grade, vascular invasion and shortened survival time in patients with lung adenocarcinoma. These data suggest that myofibroblasts are likely to facilitate the invasion and metastasis of the lung adenocarcinoma, and can be used as a?prognostic marker. Myofibroblasts may become even a?new target for treatment. Keywords: lung adenocarcinoma, myofibroblast, immunohistochemistry, prognosis.     

Mast cells correlate with angiogenesis and poor outcome in stage I lung adenocarcinoma.

Angiogenesis is in part related to mast cells. However, the biological significance of mast cells within lung carcinoma remains unclear. Immunohistochemistry was used to stain for tryptase, CD34 and vascular endothelial growth factor (VEGF) in 85 cases of stage I nonsmall cell lung carcinoma. VEGF was found in 33 of 53 adenocarcinomas and 14 of 32 squamous cell carcinomas. Cases of adenocarcinoma had significantly higher mast cell counts than those of squamous cell carcinoma. In adenocarcinoma, mast cell counts in VEGF-positive tumours were significantly higher than in VEGF-negative tumours, whereas in squamous cell carcinoma they were not. Good correlation was observed between intratumoural mast cell counts and microvessel counts. Double staining showed most intratumoural mast cells expressed VEGF. Importantly, only in lung adenocarcinoma, members in the high mast cell count group had significantly worse prognosis than those in the low mast cell count group. It is concluded that tumour-released vascular endothelial growth factors may be related to mast cell accumulation, intratumoural mast cells may produce vascular endothelial growth factor, and stromal mast cells correlate with angiogenesis and poor outcome in stage I lung adenocarcinoma.     

LKB1和VEGFR2评价肺腺癌预后的意义

目的探讨LKB1、VEGFR2在肺腺癌中的表达情况,分析其预后意义。方法应用免疫组化方法检测46例肺腺癌中LKB1、VEGFR2的表达情况。结果 LKB1在癌旁正常肺组织、淋巴结转移阴性组肺腺癌、Ⅰ～Ⅱ期肺腺癌中的表达阳性率明显高于肺腺癌组织、淋巴结转移阳性组肺腺癌和ⅢA期肺腺癌(82.61%vs 63.04%、75.00%vs 44.44%、75.00%vs35.71%),差异有统计学意义(P<0.05)。VEGFR2在癌旁正常肺组织、淋巴结转移阴性组肺腺癌、Ⅰ～Ⅱ期肺腺癌中的表达阳性率则明显低于肺腺癌组织、淋巴结转移阳性组肺腺癌和ⅢA期肺腺癌(34.78%vs 58.70%、46.43%vs 77.78%、46.88%vs85.71%),差异有统计学意义(P<0.05)。结论 LKB1、VEGFR2在肺腺癌中的表达情况可能与肺腺癌患者的预后有关,LKB1低表达、VEGFR2高表达可能提示预后不良。     

Vascular endothelial growth factor and osteopontin in stage I lung adenocarcinoma.

Tumor growth and metastasis are angiogenesis-dependent processes initiated and regulated by a number of cytokines. Vascular endothelial growth factor (VEGF) is a potent angiogenic protein with a selective mitogenic effect on vascular endothelial cells. Osteopontin (OPN) induces endothelial cell migration and upregulates endothelial cell migration induced by VEGF. To clarify the cooperative role of VEGF and OPN in tumor angiogenesis, we stained VEGF, OPN, and CD34 immunohistochemically in 87 cases of stage I non-small cell lung cancer (adenocarcinoma, 55, and squamous cell carcinoma, 32). Of the 87 patients studied, 27 patients had postoperative relapse and 60 patients did not. VEGF was found in 34 of 55 cases of adenocarcinomas and 14 of 32 squamous cell carcinomas, and OPN was found in 30 of 55 adenocarcinomas and 10 of 32 squamous cell carcinomas. In adenocarcinoma, microvessel counts of VEGF-positive and OPN-positive tumors were significantly higher than VEGF-negative and OPN-negative tumors, respectively, whereas in squamous cell carcinoma they were not. More importantly, patients with VEGF- and OPN-positive stage I lung adenocarcinoma had significantly worse prognosis as compared with other groups. Cooperation of OPN is important in VEGF-mediated tumor angiogenesis in stage I lung adenocarcinoma.     

Fascin as a useful marker for cancer-associated fibroblasts in invasive lung adenocarcinoma

Cancer-associated fibroblasts (CAFs) have been attracting attention in recent years, but their nature has not been fully elucidated. Although CAFs have been recognized as an important therapeutic target, therapeutic agents have not been developed to date. CAFs are characterized by their high migration rate and involvement in epithelial-to-mesenchymal transition with some displaying a dendritic morphology that is reminiscent of fascin expression.The present study was designed to immunohistochemically investigate fascin expression in lung adenocarcinoma including CAFs and compare the results with existing CAF markers.We immunohistochemically investigated fascin expression in not only cancer tissue but also CAFs from 26 autopsy cases of lung adenocarcinoma. Immunohistochemistry of α-smooth muscle actin and fibroblast activation protein was also performed.Fascin-positive staining in CAFs was observed in all cases, with a strong correlation observed with existing CAF markers α-smooth muscle actin and fibroblast activation protein (P < .001). In addition, the proportion of tumor cells showing fascin-positive staining was found to correlate with its expression in CAFs (P < .05).We propose that CAFs express fascin, and that fascin may mediate crosstalk between cancer tissue and CAFs. Fascin might be a novel therapeutic target for treatments that target the cancer stroma.     

Prognostic factors related with survival in patients with pancreatic adenocarcinoma

The prognosis in patients with pancreatic cancer is poor and this cancer is the fourth leading cause of cancer-related death worldwide. Although surgical resection is the only curative treatment of choice for pancreatic cancer, the majority of patients are diagnosed at an advanced stage, thus only 10%-15% of them are suitable for curative resection and the overall survival is less than 5%. Chemotherapy for metastatic disease is to palliate symptoms of patients and to improve survival. Therefore, prognostic factors are important and a correct definition of poor prognostic factors may help to guide more aggressive adjuvant or aggressive treatment protocols in patients with pancreatic cancer. This article reviews the prognostic factors affecting survival of patients with pancreatic cancer in the light of recent advances in the literature.     

Cytologic findings in stage I adenocarcinoma of the lung: Implications for the detection of early lung cancer

Preoperative cytologic examinations were performed on bronchial material from 92 patients with postsurgical (pathologic) stage I (American Joint Committee) adenocarcinoma of the lung. All patients were followed up for at least 5 years or until death; thus, cases of adenocarcinoma metastatic to the lungs were virtually excluded. Only 22 patients (24%) had abnormal preoperative cytologic findings. This low cytologic sensitivity is ascribed to the small size and peripheral location of the tumors. Large lesions of high histologic grades were more likely to have positive preoperative cytologic findings than small, well-differentiated ones.     

Prediction model on disease recurrence for low risk resected stage I lung adenocarcinoma

Background and Objective

Although stage I non-small cell lung carcinoma (NSCLC) typically carries a good prognosis following complete resection, early disease recurrence can occur. An accurate survival prediction model would help refine a follow-up strategy and personalize future adjuvant therapy. We developed a post-operative prediction model based on readily available clinical information for patients with stage I adenocarcinoma.

Methods

We retrospectively studied the disease-free survival (DFS) of 408 patients with pathologically confirmed low-risk stage I adenocarcinoma of lung who underwent curative resection from 2013 to 2017. A tree-based method was employed to partition the cohort into subgroups with distinct DFS outcome and stepwise risk ratio. These covariates were included in multivariate analysis to build a scoring system to predict disease recurrence. The model was subsequently validated using a 2011–2012 cohort.

Results

Non-smoker status, stage IA disease, epidermal-growth factor receptor mutants and female gender were associated with better DFS. Multivariate analysis identified smoking status, disease stage and gender as factors necessary for the scoring system and yielded 3 distinct risk groups for DFS [99.4 (95% CI 78.3–125.3), 62.9 (95% CI 48.2–82.0), 33.7 (95% CI 24.6–46.1) months, p < 0.005]. External validation yielded an area under the curve by receiver operating characteristic analysis of 0.863 (95% CI 0.755–0.972).

Conclusion

The model could categorize post-operative patients using readily available clinical information, and may help personalize a follow-up strategy and future adjuvant therapy.     

Prognostic factors and patients’ profile in treated stage I and II lung adenocarcinoma: a Hospital’s Cancer Registry-based analysis

BackgroundIt is known that survival from lung cancer can differ between countries and even between different regions of the same country. The variability between hospitals, the age and social profile, and the time when this patient was treated, can influence survival, and these factors are intrinsic to each region. Knowing the profile of patients, hospitals, and other factors associated with the treatment of stage I and II lung cancer in a given region is important to understand outcomes and propose improvements that can be replicated in any region of the world that presents the same profile of patients and care structure. This study evaluates survival and possible predictors in all patients with stage I and II lung cancer adenocarcinoma through the Hospital’s Cancer Registry (HCR), responsible for the State of Sao Paulo’s cancer registry, a geographical area with 40 million inhabitants.MethodsBased on the HCR, an observational study was conducted, including 1,278 patients diagnosed with lung adenocarcinoma at clinical stages (CS) I and II. Sex, age at diagnosis, education, neighbourhood, CS at diagnosis, the time between diagnosis and treatment, 5-year periods in which patients were treated, treatment modality and hospitals where patients were treated were analysed. Cox univariate and multiple regression analyses were used to estimate the hazard ratio (HR).ResultsA total of 1,278 lung cancer patients with clinical lung cancer adenocarcinoma stages I and II were included. About 40.06% of patients did not receive surgery, and only 55.8% started the treatment within 2 months. The majority of the patients were treated in high complexity hospitals, 69%. Five-year overall survival (OS) was 45.6% in CS I and 27.5% in CS II. Patients treated in high complexity centres have lower mortality rates than those treated in Partial Hospital Complexity Centers in Oncology (PHCCO) (adjHR 1.18; 95% CI: 1.00–1.40; P=0.047). Patients diagnosed between 2010–2014 had a protective factor against the risk of death concerning patients diagnosed between 2000–2004.ConclusionsThe 5-year OS has significantly improved as long as the 5-year group analysed. Also, the 5-year OS of the patients treated in high complexity hospitals is higher than those treated in PHCCO.     

The role of omentectomy during the surgical staging in patients with clinical stage I endometrioid adenocarcinoma

OBJECTIVE: The aim of this study was to evaluate whether omentectomy should be a routine part of staging surgery in endometrioid adenocarcinoma. METHODS: A retrospective study was performed on 65 patients who were primarily treated by total abdominal hysterectomy, salpingo-oophorectomy, bilateral pelvic and para-aortic lymphadenectomy, infracolic omentectomy and peritoneal cytology for clinical stage I endometrial carcinoma between January 2002 and December 2005. Data on 65 patients who had been diagnosed with clinical stage I endometrial carcinoma were reviewed. Associations in the data obtained, pelvic and para-aortic lymph node status, depth of myometrial invasion, grade, vascular invasion, adnexal involvement, positive peritoneal cytology, lymph node metastasis, cervical stromal invasion, and tumor size, were investigated. The Chi-square (chi(2)) test was used for statistical analysis. Multivariate analysis was performed with logistic regression analyses. RESULTS: Four (6.2%) of 65 patients had omental metastasis, which was microscopic in two patients. As for extrauterine spread, the positivity rate of lymph node metastases was 10/65 (15.38%), peritoneal cytology was 7/65 (10.76%), and adnexal metastases was 10/65 (15.38%). Of those patients with omental metastasis, 2/10(20%) had positive nodes, 2/10(20%) had adnexal metastases, and 3/7(42.8%) had positive peritoneal cytologic findings. These four patients with omental metastasis had significantly higher rates of positive cytology (P = 0.003). Multivariate analysis revealed omental metastasis (P = 0.002; OR 46.5, CI 95% 3.899-554.575) to be significantly associated with positive peritoneal cytology CONCLUSIONS: We conclude that despite the presence of normal-appearing omentum, omentectomy should be performed as a component of surgical staging in the presence of positive peritoneal cytology.     

Vessel invasion as a predictive factor for recurrence after surgery in stage I lung adenocarcinoma

BackgroundPatients with early-stage lung cancer who underwent R0 resection often encounter disease recurrence, especially during the early phase; thus, it is deemed vital to determine the predictive factors for recurrence after surgery. In this study, we aimed to identify the independent variables associated with recurrence after complete surgical resection of pathological stage I lung adenocarcinoma.MethodsWe retrospectively reviewed the medical records of 169 patients who underwent pulmonary resection for primary lung adenocarcinoma pathological stage I with curative intent lung cancer surgery from 2015 to December 2018 at our institution for information on the recurrence of the disease.ResultsPer the multivariate analysis, the presence of micropapillary pattern and vessel invasion were found to be independent predictors of disease recurrence after surgery (odds ratio [OR]: 9.36, 95% confidence interval [CI]: 2.42–36.2, P = 0.0012; and OR: 4.50, 95% CI: 1.52–13.4, P = 0.0068, respectively). Vessel invasion was also found to be an independent predictor of disease recurrence after surgery within a year (OR 11.4, 95% CI 3.08–42.5, P = 0.0003).ConclusionsThe presence of vessel invasion may help in distinguishing patients with the highest risk of early-phase disease recurrence after surgery. Patients with stage I adenocarcinoma with vessel invasion should undergo intensive surveillance after surgery.     

Prognostic impact of pathologically confirmed rib invasion in patients with lung cancer requiring chest wall resection

BackgroundPrimary lung cancer that invades the chest wall is classified as T3 regardless of the depth of invasion. This study assessed the prognostic impact of pathologically confirmed rib invasion in patients with pT3N0-1 lung cancer requiring chest wall resection.MethodsWe retrospectively analyzed the records of patients with non-small cell lung cancer (NSCLC) who underwent combined lung and chest wall resection with rib involvement from 2006 to 2019. The median follow-up period was 64.0 months.ResultsIn total, 42 patients (41 men, 1 woman) were enrolled. The median patient age was 64 years (range, 42–79 years). The median tumor size before treatment was 56.5 mm (range, 21–80 mm), and an osteolytic sign was identified on computed tomography (CT) in 42.9% (18/42). Among 27 patients who received induction chemoradiotherapy, 5 (18.5%) achieved a complete pathological response. The operations comprised 36 lobectomies, 5 segmentectomies, and 1 wedge resection with resection of 2.5 ribs on average. Pathological examination revealed rib invasion in 18 (42.9%) patients. The 5-year disease-free and overall survival rates with pathological rib invasion were 44.4% and 77.4% (P=0.0114), respectively and those without pathological rib invasion were 44.7% and 81.3% (P=0.0222), respectively. Pathologically confirmed rib invasion was the only factor identified to have a prognostic impact in the univariate and multivariate analyses [hazard ratio (HR), 5.98; 95% confidence interval (CI): 1.37–26.1]. Locoregional recurrence and distant metastases were more common in patients with than without pathologically confirmed rib invasion [4 (22.2%) and 6 (33.3%), respectively, among 18 patients with pathological rib invasion; 2 (8.3%) and 3 (12.5%), respectively, among 24 patients without pathological rib invasion] (P=0.0073).ConclusionsPathologically confirmed rib invasion was found to have a significant unfavorable prognostic impact in patients with pT3N0-1 lung cancer requiring chest wall resection. Multimodal therapy may be preferable in these patients to prevent local and distant relapse.     

Prognostic value of vertebral lesions detected by magnetic resonance imaging in patients with stage I multiple myeloma

We assessed the role of spinal magnetic resonance imaging (MRI) and bone densitometry as prognostic factors in patients with asymptomatic stage I multiple myeloma (MM) and negative skeletal survey. 55 consecutive patients underwent spinal MRI and 41 of them underwent bone densitometry by dual-energy X-ray absorptiometry (DEXA). Spinal MRI studies showed evidence of bone marrow involvement in 17/55 patients (31%). A diffuse pattern was present in three patients and a focal pattern in 14 patients, nine of them with only one nodular lesion. During a median follow-up of 25 months, 10 patients had disease progression, 8/17 patients with abnormal MRI and 2/38 patients with normal MRI. Median time to disease progression was not reached in both groups but was significantly different for patients with normal and those with abnormal patterns on MRI (P < 0.0001). Lumbar BMD was only slightly decreased compared with normal people (median lumbar Z score -0.43) and was not of prognostic value. Using a multivariate analysis the only two independent significant prognostic parameters were abnormal MRI (P<0.001, HR 30.4, 95% CI 4.3-213) and bone marrow plasmacytosis >20% (P=0.004, HR 16.4, 95% Cl 2.6-104). Thus, spinal MRI but not bone densitometry, appeared to be justified in patients with stage I asymptomatic MM and negative skeletal survey.