IRF8 deficiency-induced myeloid-derived suppressor cell promote immune evasion in lung adenocarcinoma.

BACKGROUND: Patients with lung adenocarcinoma (LUAD) have a low response rate to immune checkpoint blockade. It is highly important to explore the tumor immune escape mechanism of LUAD patients and expand the population of patients who may benefit from immunotherapy. METHODS: Based on 954 bulk RNA-seq data of LUAD patients and 15 single-cell RNA-seq data, the relationships between tumor immune dysfunction and exclusion (TIDE) scores and survival prognosis in each patient were calculated and evaluated, and the immune escape mechanism affecting the independent prognosis of LUAD patients was identified. Functional enrichment analysis explored the antitumour immune response and biological behavior of tumor cells among different LUAD groups. Single-cell annotation and pseudotemporal analysis were used to explore the target molecules and immune escape mechanisms of LUAD. RESULTS: Myeloid-derived suppressor cells (MDSCs) and IRF8 were identified as risk and protective factors for the independent prognosis of LUAD patients, respectively. In the tumor microenvironment of patients with high infiltration of MDSCs, the antitumor immune response is significantly suppressed, while tumor cell division, proliferation, and distant metastasis are significantly enhanced. Single-cell RNA-seq analysis revealed that IRF8 is an important regulator of MDSC differentiation in LUAD myeloid cells. In addition, IRF8 may regulate the differentiation of MDSCs through the IL6-JAK-STAT3 signalling pathway. CONCLUSIONS: IRF8 deficiency impairs the normal development of LUAD myeloid cells and induces their differentiation into MDSCs, thereby accelerating the immune escape of LUAD cells. IRF8-targeted activation to inhibit the formation of MDSCs may be a new target for immunotherapy in LUAD.

Development and validation of a clinical decision tool for preoperative micropapillary and solid pattern lung adenocarcinoma of CT≤2 cm.

BACKGROUND: Micropapillary (MP) and solid(S) pattern adenocarcinoma are highly malignant subtypes of lung adenocarcinoma. In today's era of increasingly conservative surgery for small lung cancer, effective preoperative identification of these subtypes is greatly important for surgical planning and long term survival of patients. METHODS: For this retrospective study, the presence of MP and/or S was evaluated in 2167 consecutive patients who underwent surgical resection for clinical stage IA1-2 lung adenocarcinoma. MP and/or S pattern-positive patients and negative-pattern patients were matched at a ratio of 1:3. The Lasso regression model was used for data dimension reduction and imaging signature building. Multivariate logistic regression was used to establish the predictive model, presented as an imaging nomogram. The performance of the nomogram was assessed based on calibration, identification, and clinical usefulness, and internal and external validation of the model was conducted. RESULTS: The proportion of solid components (PSC), Sphericity, entropy, Shape, bronchial honeycomb, nodule shape, sex, and smoking were independent factors in the prediction model of MP and/or S lung adenocarcinoma. The model showed good discrimination with an area under the ROC curve of 0.85. DCA demonstrated that the model could achieve good benefits for patients. RCS analysis suggested a significant increase in the proportion of MP and/or S from 11% to 48% when the PSC value was 68%. CONCLUSION: Small MP and/or S adenocarcinoma can be effectively identified preoperatively by their typical 3D and 2D imaging features.

Computed tomography imaging and clinical characteristics of pulmonary ground-glass nodules ≤2 cm with micropapillary pattern.

BACKGROUND: The aim of this study was to investigate the imaging features, lymph node metastasis, and genetic mutations in micropapillary lung adenocarcinoma (imaging with mixed ground-glass nodules) ≤2 cm, to provide a more precise and refined basis for the selection of lung segment resection. METHODS: A retrospective analysis of 162 patients with surgically resected pathologically confirmed cancers ≤2.0 cm in diameter (50 cases of micropapillary mixed ground-glass nodules [mGGNs], 50 cases of nonmicropapillary mGGNs, and 62 cases of micropapillary SNs [solid nodules]) was performed. mGGNs were classified into five categories according to imaging features. The distribution of these five morphologies in micropapillary with mGGN and nonmicropapillary with mGGN was analyzed. The postoperative pathology and prognosis of lymph node metastasis were also compared between micropapillary mGGNs and micropapillary with SNs. After searching the TCGA database, we demonstrated heterogeneity, high malignancy and high risk of microcapillary lung cancer cancers. RESULTS: Different pathological subtypes of mGGN differed in morphological features (p < 0.05). The rate of lymph node metastasis was significantly higher in micropapillary mGGNs than in nonmicropapillary mGGNs. In the TCGA database samples, lactate transmembrane protein activity, collagen transcription score, and fibroblast EMT score were remarkably higher in micropapillary adenocarcinoma. Other pathological subtypes had a better survival prognosis and longer disease-free survival compared with micropapillary adenocarcinoma. CONCLUSION: mGGNs ≤2 cm with a micropapillary pattern have a higher risk of lymph node metastasis compared with SNs, and computed tomography (CT) imaging features can assist in their diagnosis.

Expression and clinical significance of CD31, CD34, and CD105 in pulmonary ground glass nodules with different vascular manifestations on CT.

Blood vessel passage on CT exerts a vital part in early diagnosis as well as treatment of carcinoma of the lungs. Intratumoral microvascular density (iMVD) has gradually become the focus of research on biological behavior, appearance, and evolution of malignant tumors nowadays. The aim of this paper was to verify whether there is a correlation between the iMVD and the vascular morphology of ground glass nodules (GGNs). A total of 109 patients with pulmonary GGN were classified into three groups (I,II, and III) according to the vascular morphology on CT, and their expression of CD31-, CD34-, and CD105-labeled iMVD was detected by the streptoavidin-biotin method, statistically analyzing the iMVD values of each group. The expression of CD31, CD34, and CD105 in different lung tissues was significantly different, with remarkably higher iMVD in lung cancer tissues than in adjacent normal lung tissues. In the imaging sort of types I, II, and III according to the means of vascular passage, the iMVD expression of CD31, CD34, and CD105 was significantly different between groups. These data suggest that the presence and the abnormal morphology of vessels seen within GGNs indicate the occurrence and progression of lung cancer in pathology. It offers a strong theoretical foundation for early diagnosis of carcinoma of the lungs, thus providing a more precise clinical diagnosis and prognosis of early-stage lung cancer.

Screening and clinical significance of lymph node metastasis-related genes within esophagogastric junction adenocarcinoma.

BACKGROUND: Despite recent improvements in treatment technologies, such as surgical resection and chemoradiotherapy, the prognosis of patients with esophagogastric junction adenocarcinoma (EJA) remains poor due to early lymph node metastasis. Since few studies have investigated genes associated with lymph node metastasis in EJA, we aimed to screen lymph node metastasis-associated genes and clarify their expression status and prognostic significance in EJA. METHODS: The differential frequency of mutations between carcinoma and para-carcinoma tissues from 199 cases with EJA was detected using targeted next-generation sequencing (tNGS). Following a stratified analysis to determine that gender has no effect on the frequency of gene mutations, lymph node metastasis-related genes, including CDK6, MET, NOTCH1, and LRP1B, were screened, and CDK6 and LRP1B were selected for further study as they displayed significant differences in mutation rates. Differences in their expression status were verified using immunohistochemical (IHC) staining in 18 CDK6- and 17 LRP1B-mutated samples and a randomly matched control group. RESULTS: tNGS revealed that CDK6 and LRP1B mutation frequencies were significantly different between EJA cases with (N ≥ 1) or without (N = 0) lymph node metastasis. In particular, CDK6 mutation frequency was expected less, whereas that of LRP1B was remarkably higher in cases with stage N0 than in those with stage N ≥ 1. IHC staining confirmed significant differences in CDK6 and LRP1B expression status between the study and control cohorts. Chi-square tests revealed that a high CDK6 expression status correlated significantly with smoking history (p = 0.044), T stage (p = 0.035), N stage (p = 0.000), and advanced TNM stage (p = 0.001) in EJA, whereas a high LRP1B expression status only correlated with BMI (p = 0.013) and N stage (p = 0.000). Furthermore, as confirmed by survival status investigation, a high LRP1B expression status predicted good prognosis, and a high CDK6 expression status was an independent predictor of poor prognosis in patients with EJA. CONCLUSIONS: Taken together, the findings of this study demonstrate that a high CDK6 and LRP1B expression status promotes and inhibits lymph node metastasis in patients with EJA, respectively, suggesting that both CDK6 and LRP1B are significantly potential predictors of lymph node metastasis and prognosis in EJA.

The arterial-ligation-alone method for identifying the intersegmental plane during thoracoscopic anatomic segmentectomy.

BACKGROUND: Currently, methods for identifying the intersegmental plane during anatomical segmentectomy can be classified into 2 categories: the bronchial method and the vascular method. One of the vascular methods, the arterial-ligation-alone method, has not yet been validated or objectively evaluated in a large case series. We thus aimed to confirm that the arterial-ligation-alone method could effectively and accurately identify the intersegmental plane. METHODS: We retrospectively reviewed the records of 104 patients who were scheduled for thoracoscopic anatomic segmentectomy. Preoperative three-dimensional (3D) reconstruction was performed on all the affected lungs to distinguish the targeted segmental arteries, veins and bronchi. The procedure was as follows: first, based on the 3D reconstruction of the lung, the targeted segmental arteries were distinguished and ligated. Second, bilateral pulmonary ventilation was performed with pure oxygen. When the affected lung had completely inflated, contralateral pulmonary ventilation was performed. After waiting for some time, the first intersegmental plane could be obtained, and the time was recorded as T1, with an electric coagulation hook being used for marking. Thirdly, when the targeted segmental veins and bronchi had been ligated, the second intersegmental plane could be obtained by the inflation-deflation method as before, with the waiting time being recorded as T2. The differences between the 2 intersegmental planes were evaluated by 2 experienced chief thoracic surgeons. RESULT: In a total of 99 (95.2%) patients, the intersegmental planes were successfully and accurately identified by the arterial-ligation-alone method. Ultimately, 85 (81.7%) patients underwent thoracoscopic anatomic segmentectomy. The results for evaluating the differences between the 2 planes were as follows: completely consistent (94 cases, 94.9%), basically consistent (5 cases, 5.1%), and discrepant (0 cases, 0%). The mean T1 was 13.6±2.7 minutes (range, 8-25 minutes), and the mean T2 was 13.0±2.6 minutes (range, 8-23 minutes), with P=0.100 (95% CI). For 99 patients, the mean nodule size was 1.1±0.34 cm. In the 85 patients who underwent segmentectomy, the mean margin width was 2.84±0.51 cm, the mean operative duration was 165.6±18.3 minutes, the mean operative hemorrhage was 52.1±20.2 mL, and the mean duration of chest tube drainage was 3.9±1.3 days. Postoperative complications related to operative procedures occurred in 2 cases. CONCLUSIONS: The arterial-ligation-only method can effectively, accurately and inexpensively identify the intersegmental plane, and is especially suitable for the patients whose veins or bronchi are difficult to anatomize. Whether the target bronchus is ligated has no effect on the intersegmental plane.

[The value of dual time point 11C-choline PET-CT in differentiating malignant from benign lesion of mediastinum].

OBJECTIVE: To evaluate the value of dual time point 11C-choline PET-CT in differentiating malignant from benign lesions of mediastinum. METHODS: Thirty-five patients with mediastinal diseases, including 8 non-small cell lung cancer or highly suspected lung cancer patients with mediastinal lymphadenectasis, were subject to CT, dual time point PET-CT and videomediastinoscopy within four weeks. 11C-choline was used as PET tracers to visualize various masses. The imaging protocol included the first PET scanning 5-10 min after the-injection of 370 MBq 11C-choline and then a second PET scanning 25-30 min later. The PET data were evaluated using the standardized uptake value (SUV) and the difference between the two point (DeltaSUV). Then the results were analyzed in accordance with the pathologic data. RESULTS: Eleven of the 35 patients with mediastinal diseases were diagnosed as with sarcoidosis, 6 with tuberculosis, 5 with lymphoma, 11 with nodal metastasis (8 had their modes from the lung and the primary lesions of the other 3 failed to be identified), and 2 with lung cancer with reactive hyperplasia lymph node. The SUV of the delayed images of the 16 malignant lesions was 6.48 (3.0-11.2), higher than that of the early images [6.17 (3.2-9.8)] with a DeltaSUV of 0.31 (-0.4-1.4). The value of SUV of delayed images of the 19 benign lesions was 4.99 (2.2-9.3), lower than that of early images [5.11 (2.9-8.3)] with a DeltaSUV of -0.12 (-0.9-1.0). The DeltaSUV of the benign lesions was significantly lower than that of the malignant lesions (F = 1.939, P = 0.04). The accuracy rates of diagnosis of mediastinal masses of CT, first-time PET-CT, dual time point PET-CT, and videomediastinoscopy were 54.3% (19/35), 74.3% (26/35), 82.9% (29/35), and 100% (35/35) respectively. Conclusion With a high diagnostic yield, videomediastinoscopy remains the gold standard in differentiation of malignant and benign lesions located in the middle mediastinum. Dual time point PET-CT may improve the accuracy.

[The clinical application of videomediastinoscopy combined with the examination of CD(4)/CD(8) in the diagnosis of mediastinal tuberculosis and sarcoidosis].

OBJECTIVE: To evaluate the role of videomediastinoscopy combined with the examination of CD(4)/CD(8) in the diagnosis of tuberculosis and sarcoidosis of the mediastinum. METHODS: The clinical records of 90 patients who underwent videomediastinoscopy from February 2003 to September 2005 were retrospectively reviewed. The expression of CD(4)/CD(8) was studied using immunohistochemical method in the tissues from 57 cases with a diagnosis of tuberculosis or sarcoidosis and noncaseating granuloma without classical "sarcoid" pathology obtained by videomediastinoscopy. RESULTS: Sarcoidosis was diagnosed in 37 patients, tuberculosis in 14 patients, lymphoma in 15 patients, nodal metastasis in 18 patients, noncaseating granuloma without classical "sarcoid" in 6 patients. The diagnostic accuracy was 93.3% (84/90). The expression of CD(4) and CD(8) in sarcoidosis was (65 +/- 13)% and (9.4 +/- 2.6)%, respectively. While the expression of CD(4) and CD(8) in tuberculosis was (41 +/- 11)% and (11.8 +/- 3.4)%, respectively. The rate of CD(4)/CD(8) in sarcoidosis was higher than that in tuberculosis (7.3 +/- 1.8 and 3.6 +/- 1.1, respectively, t = 1.883, P = 0.000). The accuracy, specificity and sensitivity for diagnosis of sarcoidosis was 90.2%, 85.7% and 91.9%, respectively, if the cutoff value of CD(4)/CD(8) was 5. No complication or mortality was reported. CONCLUSION: Videomediastinoscopy is an effective procedure for the diagnosis of mediastinal diseases. The examination of CD(4)/CD(8) adds more information to the differentiation of tuberculosis from sarcoidosis.

[Clinical therapeutic effect of esophageal carcinoma with hand video assisted surgery].

OBJECTIVE: To explore the clinical therapeutic effect of esophageal carcinoma with hand video assisted surgery. METHODS: Forty cases which C TNM stage was T3N1M0 received hand video assisted surgery (HVATS group), 40 cases received routine operation (control group). Recurrence survival analysis of each group was analyzed with SPSS10.0 software according to the date of the stage and survival rate. RESULTS: All group have satisfied surgical result. All patients have good quality of life. The 3 year survival rate was 52.7% in HVATS group and 51.3% in control group. The difference of survival rate was no significance. CONCLUSION: Hand video assisted surgery for esophageal carcinoma had same result as routine thoracic operation. Short operation time, less trauma and fast recovery are the advantages of hand video assisted surgery.

The role of 11C-choline positron emission tomography-computed tomography and videomediastinoscopy in the evaluation of diseases of middle mediastinum.

BACKGROUND: Middle mediastinal masses comprise a wide variety of tumors but may also reflect lymphadenopathy, and thus remain an interesting diagnostic challenge. We performed positron emission tomography (PET) of mediastinal masses in order to evaluate the ability of PET to predict the malignancy of these tumors. We compared histologic findings, videomediastinoscopy, computed tomography (CT), and PET-CT in patients with mediastinal disease. METHODS: Thirty-two patients were evaluated with CT, PET-CT and videomediastionoscopy, and all studies were performed within four weeks in each patient. (11)C-choline as a PET tracer was used to visualize masses. PET data were evaluated using the standardized uptake value (SUV) and were compared with pathologic data. RESULTS: There were 13 men and 19 women aged from 21 to 74 (mean 45.2) years. Among the patients with mediastinal diseases, sarcoidosis was diagnosed in 12 patients, tuberculosis in 5 patients, lymphoma in 5 patients, and noncaseating granulomata without classical "sarcoid" finding in 3 patients. N2 or N3 nodal metastasis was revealed in 6 of 7 patients who had non-small cell lung cancer or suspected lung cancer, and one was negative (the pathological diagnosis was reactive hyperplasia). The accuracies for correctly diagnosing mediastinal masses for CT, PET-CT and videomediastinoscopy were 38% (12/32), 63% (20/32), and 91% (29/32) respectively. The diagnostic accuracy of videomediastinoscopy was superior to that of PET-CT (chi(2) = 11.130, P < 0.001). The SUVs were similar among these diseases. On the other hand, if the diagnostic classification was benign vs malignancy, the accuracies for CT, PET-CT and videomediastinoscopy were 53% (17/32), 75% (24/32), 100% (32/32) respectively. The diagnostic accuracy of videomediastinoscopy was superior to that of PET-CT (chi(2) = 22.042, P < 0.001). The SUV of malignant lesions (6.9, 3.2 - 9.8; n = 11) appeared to be higher than that of benign lesions (4.9, 2.9 - 8.3; n = 21), however, this difference was not statistically significant (P = 0.054). CONCLUSIONS: To diagnose lesions located in the middle mediastinum, videomediastinoscopy possesses the highest diagnostic accuracy, and therefore remains the gold standard. PET-CT is valuable for differential diagnosis of benign vs malignant lesions, CT alone or PET alone (SUV) may provide misdiagnosis in a substantial proportion of patients with mediastinal masses.

[Clinical value of videomediastinoscopy in diagnosis of mediastinal disease].

OBJECTIVE: To evaluate the role of videomediastinoscopy in the diagnosis of disease of the mediastinum. METHODS: We retrospectively reviewed the clinical records of the 115 patients who underwent videomediastinoscopy. Local anesthesia or general anesthesia was employed. This operation consisted of cervical videomediastinoscopy in 102 patients, parasternal videomediastinoscopy in 13 patients, ninety-one patients had videomediastinoscopy for diagnosis of isolated mediastinal mass or lymphadenopathy, 25 patients with non small cell lung cancer or suspected lung cancer showed enlarged mediastinal lymph nodes radiographically in the chest. RESULTS: Among the patients with mediastinal disease, sarcoidosis was diagnosed in 37 patients, tuberculosis in 14 patients, lymphoma in 15 patients, nodal metastasis in 18 patients, noncaseating granulomata without classical "sarcoid" in 6 patients, with the accuracy of 93.3% (84/90); and staging of lung cancer in 25 patients, with the accuracy of 100% (25/25). The total accuracy of videomediastinoscoy and CT was 94.8% (109/115), 56.5% (65/115), respectively. Mean operative time was 26 min. There was neither complication nor mortality. CONCLUSION: videomediastinoscopy is a safe and effective procedure for the diagnosis of mediastinal disease and the staging of lung cancer.

[Resection for lung cancer invading the superior vena cava].

OBJECTIVE: To analyze the feasibility and the value of resection for lung cancer invading the superior vena cava (SVC). METHODS: Between 1988 and 2005 the data of 31 patients who underwent resection were analyzed retrospectively. The reconstruction was done using simple suture, pericardial patch or prosthetic replacement. Postoperative morbidity, long-term survival were examined using the Kaplan-Meier method (Log rank test) and the COX model for survival. RESULTS: Seventeen squamous cell carcinomas, 8 adenocarcinomas, and 6 undifferentiated small cell carcinomas were resected. There were 13 partial SVC resection, the reconstruction was done using a simple running in 5 patients, and a pericardial patch in 8 patients. Eighteen patients underwent complete resection of SVC with prosthetic replacement. The time of clamping the SVC system was from 8 to 35 minutes for complete resection patients, while the time was from 3 to 15 minutes for partial resection patients. One patient didn't clamp the SVC. Postoperative morbidity and mortality were 48% and 0%, respectively. One, 3 and 5-year survival rates were 61%, 33% and 21%, respectively, with median survival at 31 months. Survival rate of patients with N2 disease was obviously lower than those with localized (N0/N1) nodal disease (chi2 = 14.3, P = 0.000), the median survival was 42 and 13 months respectively. There were no significant effects on overall survival with pathologic features and surgery methods. Survival rate of patients with induction chemotherapy before operation or intraoperative chemotherapy was higher than those received direct surgery (chi2 = 5.0, P = 0.025), the median survival was 39 and 14 months respectively. CONCLUSIONS: The resection of the SVC for involvement by lung cancer can be performed in selected patients, especially for those with localized (N0/N1) nodal disease. Induction chemotherapy should be performed.

[Hand-assisted video-thoracoscopy for resection of esophageal cancer].

OBJECTIVE: To explore the feasibility and advantages of hand-assisted video-thoracoscopy for resection of esophageal cancer. METHODS: Forty-five patients with esophageal cancer received hand-assisted video-thoracoscopic esophagectomy (group I). 45 patients underwent esophagectomy through routine open thoracotomy during the same period as control (group II). The data of lymph node resection, operating time and blood loss were compared. RESULTS: There were no operative mortality in 2 groups. In group I, the number of dissected paraesophageal lymph nodes, cardiac lymph nodes and left gastric nodes were (3.6 +/- 1.0), (1.3 +/- 1.1) and (4.3 +/- 1.4), respectively. While for group II the dissected lymph nodes were (3.3 +/- 1.5), (1.6 +/- 1.1) and (4.7 +/- 2.1), respectively. There was no significant difference between two groups (P > 0.05). However, the number of dissected mediastinal nodes was (6.6 +/- 3.7) for group I and (3.8 +/- 2.5) for group II (chi(2) = 2.95, P < 0.05). The mean operating time was (29 +/- 5) minutes for group I and (60 +/- 6) minutes for group II. The mean blood loss was (93 +/- 19) ml for group I and (145 +/- 35) ml for group II. The mean chest tube drainage was (201 +/- 45) ml for group I and (295 +/- 57) ml for group II in the first postoperative day. The difference in above parameters between 2 groups was significant (chi(2) = 18.69, 6.13, 6.08, P < 0.001). CONCLUSIONS: It is suggested that hand-assisted video-thoracoscopic esophagectomy is a safer, minimal invasive procedure in the resection of esophagus carcinoma.

Chinese expert consensus workshop report: Guidelines for thermal ablation of primary and metastatic lung tumors.

Although surgical resection is the primary means of curing both primary and metastatic lung cancers, about 80% of lung cancers cannot be removed by surgery. As most patients with unresectable lung cancer receive only limited benefits from traditional radiotherapy and chemotherapy, many new local treatment methods have emerged, including local ablation therapy. The Minimally Invasive and Comprehensive Treatment of Lung Cancer Branch, Professional Committee of Minimally Invasive Treatment of Cancer of the Chinese Anti-Cancer Association has organized multidisciplinary experts to develop guidelines for this treatment modality. These guidelines aim at standardizing thermal ablation procedures and criteria for selecting treatment candidates and assessing outcomes; and for preventing and managing post-ablation complications.

Management of the primary malignant mediastinal germ cell tumors: experience with 54 patients.

BACKGROUND: Primary malignant mediastinal germ cell tumor (PMMGCT) is rare and sometimes the prognosis of the patients with PMMGCT is not very satisfactory. METHODS: A total of 54 patients with PMMGCT in a follow-up from 1990 to 2009. We evaluated the role of the surgical treatment and the effect of multimodality treatment strategy for patients with PMMGCT. RESULTS: Fifty-two patients underwent surgical resections, while the other two patients just received chemoradiotherapy. Among the 52 patients, 28 cases received preoperative adjuvant therapy and 24 cases underwent surgery as initial treatment; 30 cases with complete resections, 18 cases with partial resections and 4 cases with only biopsies. There was no perioperative mortality. Histopathologic results revealed 18 cases of seminomas and 36 cases of nonseminomatous germ cell tumors (NSGCT). The last follow-up showed that 17 patients were alive, including 11 patients with seminoma and 6 patients with NSGCT. The 5-year overall survival rate of patients with seminomas was 87.7%. The 3-year and 5-year overall survival rates of patients with NSGCT were 47.4% and 23.0%, respectively. CONCLUSIONS: It could be concluded that a complete surgical resection of PMMGCT after chemoradiotherapy showed favorable long-term survival. Patients with pure seminomas have a better prognosis compared with that with NSGCT. VIRTUAL SLIDES: The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1676987232116837.

[Predictive value of drug resistance-related genes expression in neoadjuvant chemotherapy in patients with non-small cell lung cancer of stage III].

BACKGROUND & OBJECTIVE: P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP), and lung resistant protein (LRP) play important roles in multidrug resistance (MDR). This study was to determine P-gp, MRP, and LRP expression in patients with non-small cell lung cancer (NSCLC) of stage III, and evaluate their predictive value in neoadjuvant chemotherapy. METHODS: Immunohistochemical analyses were performed on 31 patients with NSCLC of stage III before, and after neoadjuvant chemotherapy. RESULTS: The frequency of P-gp, MRP, and LRP expression were 29.0% (9/31), 45.2% (14/31), and 38.7% (12/31) before chemotherapy, and were 61.3% (19/31), 51.6% (16/31), and 41.9% (13/31) after chemotherapy. Of 31 patients, 10 (10/31, 32.3%) expressed both MRP and LRP before chemotherapy, which indicated significant positive correlation between MRP and LRP expression (r=0.061, P< 0.001). In patients with P-gp, MRP, or LRP expression before chemotherapy, the response rates towards chemotherapy were 44.4% (4/9), 28.6% (4/14), and 16.7% (2/12). Of 10 patients with both MRP and LRP expression, only 1 (1/10, 10.0%) responded to chemotherapy. The median survival time of patients who responded to chemotherapy was 31 months, while that of patients who did not responded to chemotherapy was 15 months, that of patients who didn't receive neoadjuvant chemotherapy before surgery was 18 months. CONCLUSION: Patients with both MRP and LRP expression are probably resistant to chemotherapy, the value of neoadjuvant chemotherapy is limit in such patients.