[Clinical value of a differentiation prediction model for invasive lung adenocarcinoma].

Objective: To investigate the value of predicting the degree of differentiation of pulmonary invasive adenocarcinoma (IAC) based on CT image radiomics model and the expression difference of immunohistochemical factors between different degrees of differentiation of lesions. Methods: The clinicopathological data of patients with pulmonary IAC confirmed by surgical pathology in the Affiliated Huai'an First People's Hospital to Nanjing Medical University from December 2017 to September 2018 were collected. High-throughput feature acquisition was performed for all outlined regions of interest, and prediction models were constructed after dimensionality reduction by the minimum absolute shrinkage operator. Receiver operating characteristic curve was used to assess the predictive efficacy of clinical characteristic model, radiomics model and individualized prediction model combined with both to identify the degree of pulmonary IAC differentiation, and immunohistochemical expressions of Ki-67, NapsinA and TTF-1 were compared between groups with different degrees of IAC differentiation using rank sum test. Results: A total of 396 high-throughput features were extracted from all IAC lesions, and 10 features with high generalization ability and correlation with the degree of IAC differentiation were screened. The mean radiomics score of poorly differentiated IAC in the training group (1.206) was higher than that of patients with high and medium differentiation (0.969, P=0.001), and the mean radiomics score of poorly differentiated IAC in the test group (1.545) was higher than that of patients with high and medium differentiation (-0.815, P<0.001). The differences in gender (P<0.001), pleural stretch sign (P=0.005), and burr sign (P=0.033) were statistically significant between patients in the well and poorly differentiated IAC groups. Multifactorial logistic regression analysis showed that gender and pleural stretch sign were related to the degree of IAC differentiation (P<0.05). The clinical feature model consisted of age, gender, pleural stretch sign, burr sign, tumor vessel sign, and vacuolar sign, and the individualized prediction model consisted of gender, pleural stretch sign, and radiomic score, and was represented by a nomogram. The Akaike information standard values of the radiomics model, clinical feature model and individualized prediction model were 54.756, 82.214 and 53.282, respectively. The individualized prediction model was most effective in identifying the degree of differentiation of pulmonary IAC, and the area under the curves (AUC) of the individualized prediction model in the training group and the test group were 0.92 (95% CI: 0.86-0.99) and 0.88 (95% CI: 0.74-1.00, respectively). The AUCs of the radiomics group model for predicting the degree of differentiation of pulmonary IAC in the training group and the test group were 0.91 (95% CI: 0.83-0.98) and 0.87 (95% CI: 0.72-1.00), respectively. The AUCs of the clinical characteristics model for predicting the degree of differentiation of pulmonary IACs in the training and test groups were 0.75 (95% CI: 0.63-0.86) and 0.76 (95% CI: 0.59-0.94), respectively. The expression level of Ki-67 in poorly differentiated IAC was higher than that in well-differentiated IAC (P<0.001). The expression levels of NapsinA, TTF-1 in poorly differentiated IAC were higher than those in well-differentiated IAC (P<0.05). Conclusions: Individualized prediction model consisted of gender, pleural stretch sign and radiomics score can discriminate the differentiation degree of IAC with the best performance in comparison with clinical feature model and radiomics model. Ki-67, NapsinA and TTF-1 express differently in different degrees of differentiation of IAC.

[Expression of TTF-1, NapsinA, P63, CK5/6 in Lung Cancer and Its Diagnostic Values for Histological Classification].

OBJECTIVES: To investigate the expressions of thyroid transcription factor-1(TTF-1), NapsinA, P63 and CK5/6 in lung cancer tissues and their diagnostic value for histological classification. METHODS: The protein expression in a total of 964 lung cancer samples was detected by immunohistochemistry, of which 929 cases for TTF-1, 113 cases for NapsinA, 282 cases for P63, and 277 for CK5/6, respectively. The correlations between the protein expressions of the four markers and clinicopathological features in lung cancer patients were analyzed. The area under the curves (AUCs) of ROC curves, sensitivity and specificity were calculated to determine the diagnostic values for the four markers. RESULTS: There were 552 cases of lung adenocarcinoma (ADC), 146 cases of lung squamous cell carcinoma (SCC), 253 cases of small cell carcinoma (SCLC), and 13 cases of large cell carcinoma (LCC). The median age was 56 years old, and 63.4% was male. The positive expression rates of TTF-1, NapsinA, P63, and CK5/6 were 76.3% (709/929), 67.3% (76/113) , 47.2% (133/282) and 34.7% (96/277), respectively. The positive expression rates of TTF-1 and NapsinA were higher in lung ADC, and the sensitivity and specificity of TTF-1 in the diagnosis of ADC were 81.15% and 30.41% respectively, those of NapsinA were 82.05% and 65.71% respectively. The AUCs for TTF-1 and NapsinA were 0.557 8 (P=0.002 6, 95%CI:0.520 0-0.595 6) and 0.738 8 (P<0.000 1, 95%CI:0.633 4-0.844 2) respectively. The positive expression rates of P63 and CK5/6 were significantly higher in lung SCC, and their sensitivities to diagnose SCC were 80.68% and 81.25%, with specificity 68.04% and 84.26% respectively. TheAUCsfor P63 and CK5/6 were 0.743 6 (P<0.000 1, 95%CI:0.681 9-0.805 3) and 0.827 6 (P<0.000 1, 95%CI:0.770 0-0.885 2) respectively. Logistic regression model with small sample (44 cases, ADC or SCC) showed that NapsinA was an independent factor to distinguish ADC and SCC (partial regression coefficient=2.826, P=0.022), while the other three markers showed no statistical significance (P>0.05). CONCLUSIONS: TTF-1 and NapsinA can be used as prognositic markers for lung ADC. P63 and CK5/6 can be used as prognostic markers for lung SCC. NapsinA may be used to distinguish ADC and SCC.

Aberrant Expression of Pneumocytic Markers (TTF-1 and Napsin-A) in Biliary Duct and Gallbladder Adenocarcinomas; A Potential Diagnostic Pitfall.

Cholangiocarcinomas and gallbladder carcinomas are epithelial tumours with biliary differentiation. On histology and immunohistochemistry, they resemble adenocarcinomas and possess overlapping immunohistochemical profiles. Diagnosing these tumours is best done using appropriate imaging and clinical features with compatible immunohistochemistry. Immuno-staining for thyroid transcription factor-1 (TTF-1) and novel aspartic proteinase of pepsin A (Napsin-A) is believed to be specific for primary pulmonary adenocarcinomas. We herein report uncommon instances of strong and diffuse expression of these markers in two examples of adenocarcinomas arising from the bile duct and gallbladder. A review of the literature and a summary of similar studies relating to aberrant TTF-1 and Napsin-A expression in biliary tract adenocarcinomas are presented.

Identification of the most specific markers to differentiate primary pulmonary carcinoma from metastatic gastrointestinal carcinoma to the lung.

BACKGROUND: A number of biomarkers have the potential of differentiating between primary lung tumours and secondary lung tumours from the gastrointestinal tract, however, a standardised panel for that purpose does not exist yet. We aimed to identify the smallest panel that is most sensitive and specific at differentiating between primary lung tumours and secondary lung tumours from the gastrointestinal tract. METHODS: A total of 170 samples were collected, including 140 primary and 30 non-primary lung tumours and staining for CK7, Napsin-A, TTF1, CK20, CDX2, and SATB2 was performed via tissue microarray. The data was then analysed using univariate regression models and a combination of multivariate regression models and Receiver Operating Characteristic (ROC) curves. RESULTS: Univariate regression models confirmed the 6 biomarkers' ability to independently predict the primary outcome (p < 0.001). Multivariate models of 2-biomarker combinations identified 11 combinations with statistically significant odds ratios (ORs) (p < 0.05), of which TTF1/CDX2 had the highest area under the curve (AUC) (0.983, 0.960-1.000 95% CI). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 75.7, 100, 100, and 37.5% respectively. Multivariate models of 3-biomarker combinations identified 4 combinations with statistically significant ORs (p < 0.05), of which CK7/CK20/SATB2 had the highest AUC (0.965, 0.930-1.000 95% CI). The sensitivity, specificity, PPV, and NPV were 85.1, 100, 100, and 41.7% respectively. Multivariate models of 4-biomarker combinations did not identify any combinations with statistically significant ORs (p < 0.05). CONCLUSIONS: The analysis identified the combination of CK7/CK20/SATB2 to be the smallest panel with the highest sensitivity (85.1%) and specificity (100%) for predicting tumour origin with an ROC AUC of 0.965 (p < 0.001; SE: 0.018, 0.930-1.000 95% CI).

Automated Immunohistochemistry Assay for the Detection of Napsin-A in Formalin-Fixed Paraffin-Embedded Tissues from Lung Tumors.

Immunohistochemistry (IHC) enables the selective detection of proteins in cells of formalin-fixed-paraffin-embedded (FFPE) tissue sections. This technique plays a key role in the identification and classification of primary lung cancer tumors through the evaluation of the expression of the aspartic proteinase Napsin-A. However, immunohistochemistry is a complex process involving many critical steps and the lack of standardization as well as inappropriate analytical conditions may contribute to inconsistent results between laboratories. Automated immunohistochemistry addresses this issue by ensuring the quality and the reproducibility of the results among different laboratories. Here we describe an automated IHC protocol used in our laboratory for the detection of Napsin-A in FFPE lung tissue sections.

Napsin-A Expression, a Reliable Immunohistochemical Marker for Diagnosis of Ovarian and Endometrial Clear Cell Carcinomas.

BACKGROUND & OBJECTIVE: Clear cell carcinomas (CCC) differ from other types of ovarian and endometrial carcinomas in biology, behavior and response to chemotherapy. Histopathologic diagnosis may be challenging in some situations which necessitates immunohistochemistary (IHC) assessment. In this study we investigated the diagnostic utility of Napsin-A in diagnosis of ovarian and endometrial CCCs. METHODS: Ovarian and endometrial CCC samples from 2013 to 2018 in 3 general and women's hospital in Tehran were re-evaluated by 2 expert pathologists. Forty-two samples were included as case and 42 non-clear cell carcinomas (Non-CCC) of ovary and endometrium were selected as control group. Based on IHC study tumors with sum intensity and percentage score ≥2 (at least 1+ staining in more than 1% of tumor cells) were considered positive. RESULTS: The prevalence of endometrial and ovarian CCC in the case group were 15 and 27 respectively. The tumors in the control group included 22 cases of endometrioid, 2 high grade papillary serous carcinoma (HGSC) of endometrium, 6 endometrioid and 12 HGSC of ovary. Napsin-A positivity was observed in 35 (83%) of CCCs while 7 (17%) samples including 3 out of 15 endometrial and 4 out of 27 ovarian CCCs were Napsin-A negative. No positive reaction was seen in control group. The overall accuracy, specifity and sensitivity of Napsin-A for diagnosis of ovarian and endometrial CCCs were 83%, 100% and 83%, respectively. Sensitivity for ovarian and endometrial CCCs were 85% and 80%, orderly. CONCLUSION: Napsin-A is an accurate and reliable marker for distinction of CCCs from non-CCCs in ovary and endometrium. A panel of antibodies may yield the highest diagnostic accuracy.

Bone metastasis of papillary thyroid carcinoma simulating a pulmonary origin. Unusual immunohistochemistry leading to misdiagnosis.

Immunophenotypical features from tumors can be variable and, sometimes, confusing. We herein report a 61 year old woman with two foci of papillary thyroid microcarcinoma who developed a bone lesion four months after total thyroidectomy/central lymphadenectomy (mpT1aN0), with an immunohistochemical pattern suggestive of a pulmonary rather than a thyroid origin (CK7, napsin-A and TTF1 positive; and negative thyroglobulin). Further biomarkers (HBME-1 and PAX8) were performed in order to confirm primary tumor, leading to conclusion of a bone metastasis from thyroid papillary carcinoma. We believe it is always advisable to perform more than one biomarker as part of a panel to get a more reliable diagnosis.

Expression of alpha-methylacyl-CoA racemase in vaginal gastric-type adenocarcinoma and uterine clear cell carcinoma.

BACKGROUND: Alpha-methylacyl-coenzyme A racemase (AMACR, P504S) is a commonly used marker in immunohistochemical diagnosis of prostate cancer. Recent studies identified P504S markers of the clear cell histotype in the ovary and/or endometrium. Gastric-type adenocarcinoma (GAS) is difficult to diagnose histologically, particularly when there is crossover with clear cell carcinoma (CCC). However, the significance of P504S for differentially diagnosing GAS and CCC is unclear. AIM: To evaluate P504S as a potential diagnostic marker of GAS and CCC. SETTINGS AND DESIGN: We analyzed P504S expression in 48 cervical carcinomas (32 GAS and 16 CCC), as well as the expression of other markers including hepatocyte nuclear factor-1 beta (HNF-1ß) and NapsinA. MATERIAL AND METHODS: The expression differences of HNF-1ß, NapsinA, and P504S in GAS and CCC were detected by immunohistochemistry. Immunohistochemical histoscores based on the intensity and extent of staining were calculated. RESULTS: The positive rates of HNF-1ß in GAS and CCC were 90.32% and 75%, respectively. (χ2 = 2.251, P = 0.663). The positive rates of NapsinA in GAS and CCC were 19.36% and 81.25%, respectively. (χ2 = 47.332, P < 0.01). The positive rates of P504S in GAS and CCC were 16.13% and 81.25%, respectively. (χ2 = 41.420, P < 0.01). HNF-1ß was frequently expressed in GAS and CCC, while NapsinA and P504S were frequently expressed in CCC, and reduced or lost in GAS. CONCLUSION: NapsinA and P504S can be used to differentiate between GAS and CCC.

Primary peritoneal clear cell carcinoma. A case report and literature review.

Primary peritoneal malignant tumors are exceptional. Among them, clear cell carcinoma is extremely rare, being only thirteen cases previously reported in the literature since 1990. We report a case of a 48-year-old Caucasian woman who was treated at the University General Hospital of Alicante. She consulted because of progressive abdominal pain over the last seven months, with the initial diagnosis of renal-ureteral colic. Ultrasound and computed tomography of the abdomen and pelvis revealed a 25 × 15 cm, well-defined cystic lesion with papillary projections, centrally located in the abdomen. The radiology report suggested a primary ovarian tumor versus peritoneal implant as the first option. The patient underwent an exploratory laparotomy showing a large cystic mass located in the urinary bladder peritoneum, firmly attached to the mesentery. The entire abdominal tumor was completely excised, and total hysterectomy with bilateral salpingo-oophorectomy and infra-colical omentectomy were performed. The final histological study revealed a new case of primary peritoneal clear cell carcinoma located in the urinary bladder peritoneum, firmly attached to the mesentery. Grossly, it was well-circumscribed and multicystic with papillary growth involving part of the inner wall. Microscopically, it showed tubulocystic and papillary patterns with highly atypical tumor cells. After an extensive immunohistochemical analysis, the most relevant finding was an ARID1A loss that was corroborated by molecular analysis showing an ARID1A deletion. The patient received systemic chemotherapy with carboplatin and paclitaxel protocol (Å ~ 4 cycles). Patient follow-up after the eighth month showed peritoneal implants predominantly in the right diaphragmatic cupule that were histologically confirmed as recurrence. She has just received another six cycles of chemotherapy with carboplatin and paclitaxel. Recognition of primary peritoneal clear cell carcinoma in this uncommon location, and exclude metastasis from the ovary, represents a diagnostic challenge.

The expression of IMP3 in 366 cases with ovarian carcinoma of high grade serous, endometrioid and clear cell subtypes.

The clear cell (CCC), high grade serous (HGSC) and endometrioid (EC) ovarian carcinomas share overlapping histological features. The oncogene IMP3 is implicated in CCC with an elusive utility in differential diagnosis. We collected 366 cases with ovarian primary carcinomas to detect IMP3, Napsin-A and HNF-1ß by immunochemistry. In 351 cases, the positive expression rate of IMP3 in CCC was significantly higher than that either in EC or HGSC (p < 0.01). The sensitivity of IMP3 in CCC was higher than Napsin-A but lower than HNF-1ß (p < 0.01). The specificity of IMP3 in CCC was lower than Napsin-A but higher than HNF-1ß (p < 0.01). The composite markers Napsin-A+/IMP3+ and the IMP3+/HNF-1ß+/Napsin-A+ offered the highest odds ratio (p < 0.001), the highest specificity, the highest positive predictive value and the highest positive likelihood ratio. The ROC analysis showed that the combination of Napsin-A, HNF-1ß and IMP3 offered the biggest AUC compared with either the singular marker performances or the other binary combinations (p < 0.001). In 15 cases of EC mixed with CCC, IMP3 showed a better discrimination value than the other two markers. Consequently, adding IMP3 to the diagnostic panel might provide some help with the pathological diagnosis of ovarian CCC.

Clinical value of a differentiation prediction model for invasive lung adenocarcinoma / 中华肿瘤杂志

Objective: To investigate the value of predicting the degree of differentiation of pulmonary invasive adenocarcinoma (IAC) based on CT image radiomics model and the expression difference of immunohistochemical factors between different degrees of differentiation of lesions. Methods: The clinicopathological data of patients with pulmonary IAC confirmed by surgical pathology in the Affiliated Huai'an First People's Hospital to Nanjing Medical University from December 2017 to September 2018 were collected. High-throughput feature acquisition was performed for all outlined regions of interest, and prediction models were constructed after dimensionality reduction by the minimum absolute shrinkage operator. Receiver operating characteristic curve was used to assess the predictive efficacy of clinical characteristic model, radiomics model and individualized prediction model combined with both to identify the degree of pulmonary IAC differentiation, and immunohistochemical expressions of Ki-67, NapsinA and TTF-1 were compared between groups with different degrees of IAC differentiation using rank sum test. Results: A total of 396 high-throughput features were extracted from all IAC lesions, and 10 features with high generalization ability and correlation with the degree of IAC differentiation were screened. The mean radiomics score of poorly differentiated IAC in the training group (1.206) was higher than that of patients with high and medium differentiation (0.969, P=0.001), and the mean radiomics score of poorly differentiated IAC in the test group (1.545) was higher than that of patients with high and medium differentiation (-0.815, P<0.001). The differences in gender (P<0.001), pleural stretch sign (P=0.005), and burr sign (P=0.033) were statistically significant between patients in the well and poorly differentiated IAC groups. Multifactorial logistic regression analysis showed that gender and pleural stretch sign were related to the degree of IAC differentiation (P<0.05). The clinical feature model consisted of age, gender, pleural stretch sign, burr sign, tumor vessel sign, and vacuolar sign, and the individualized prediction model consisted of gender, pleural stretch sign, and radiomic score, and was represented by a nomogram. The Akaike information standard values of the radiomics model, clinical feature model and individualized prediction model were 54.756, 82.214 and 53.282, respectively. The individualized prediction model was most effective in identifying the degree of differentiation of pulmonary IAC, and the area under the curves (AUC) of the individualized prediction model in the training group and the test group were 0.92 (95% CI: 0.86-0.99) and 0.88 (95% CI: 0.74-1.00, respectively). The AUCs of the radiomics group model for predicting the degree of differentiation of pulmonary IAC in the training group and the test group were 0.91 (95% CI: 0.83-0.98) and 0.87 (95% CI: 0.72-1.00), respectively. The AUCs of the clinical characteristics model for predicting the degree of differentiation of pulmonary IACs in the training and test groups were 0.75 (95% CI: 0.63-0.86) and 0.76 (95% CI: 0.59-0.94), respectively. The expression level of Ki-67 in poorly differentiated IAC was higher than that in well-differentiated IAC (P<0.001). The expression levels of NapsinA, TTF-1 in poorly differentiated IAC were higher than those in well-differentiated IAC (P<0.05). Conclusions: Individualized prediction model consisted of gender, pleural stretch sign and radiomics score can discriminate the differentiation degree of IAC with the best performance in comparison with clinical feature model and radiomics model. Ki-67, NapsinA and TTF-1 express differently in different degrees of differentiation of IAC.

The role of Napsin-A and Desmocollin-3 in classifying poorly differentiating non-small cell lung carcinoma.

UNLABELLED: There is increased need for classification of non-small cell lung cancer (NSCLC) into its major subtypes, adenocarcinoma (AC) and squamous cell carcinoma (SCC). Such a classification is enabled in poorly differentiated tumours based on routine morphology due to overlapping morphologic features. In such cases, the use of immunohistochemistry (IHC) can differentiate between the two subtypes. PURPOSE: To test the ability of the two markers; Napsin-A and Desmocollin-3, in differentiating poorly differentiated (AC) from poorly differentiated SCC in small biopsies. PATIENTS AND METHODS: This is a retrospective study including 60 patients who presented with pulmonary nodules. Cases with biopsy specimens diagnosed as poorly differentiated non-small cell lung cancer, and had corresponding resection specimens were included. Cell blocks were stained with anti Napsin-A, and anti Desmocollin-3. Cytoplasmic immunoreactivity for both markers was considered specific. Sensitivity, specificity, positive and negative predictive values, total accuracy and combined accuracy of both markers were calculated. RESULTS: Napsin A showed a sensitivity of 89.3%, a specificity of 96.9%, PPV of 96.2%, NPV of 91.2%, and a total accuracy of 93.3% for AC, while Desmocollin-3 achieved 90.6% sensitivity, 96.4% specificity, 96.7% PPV, 90% NPV, and 93.3% total accuracy. Both markers achieved a total accuracy of 90%. CONCLUSION: Napsin-A, and Desmocollin-3 were sensitive and specific markers for the diagnosis of AC and SCC, respectively. Both markers allowed classification of 54/60 cases into either AC or SCC.

Utility of TTF-1 and Napsin-A in the work-up of malignant effusions.

BACKGROUND: Similar to TTF-1, Napsin-A is recently used increasingly to differentiate between pulmonary adenocarcinoma (P-ADC) and extra-pulmonary adenocarcinoma (EP-ADC). The aim of this study was to compare the performance of TTF-1 and Napsin-A in determining the primary origin of adenocarcinoma in malignant serous effusion. METHODS: Following IRB approval, cellblocks from 139 cases of malignant serous effusions of histologically or clinically determined origin including: 26 P-ADC, 108 EP-ADC, 2 pulmonary squamous cell carcinoma (P-SQC), and 3 pulmonary small cell carcinoma (P-SCC) were retrieved. Each case was stained with Napsin-A and TTF-1 and evaluated for positivity and intensity of staining. RESULTS: Napsin-A and TTF-1 stained positive in 17/26 (65%) and 14/26 (54%) of P-ADC and in 2/108 (1.8%) and 0/108 (0%) of EP-ADC with a PPV of 89 and 100%, respectively. In combination, they positively stained 18/26 (70%) of P-ADC with a PPV of 90%. Out of 9 poorly differentiated P-ADC, 7 (78%) stained positive for Napsin-A, while 4 (45%) were reactive for TTF-1. Both Napsin-A and TTF-1 were negative in P-SQC, while P-SCC reacted positively for TTF-1 in 2/3 (66%) of cases and none for Napsin-A. CONCLUSION: Napsin-A and TTF-1 are both useful markers in distinguishing P-ADC from EP-ADC. However, Napsin-A performed better in poorly differentiated P-ADC and its mimickers. The nuclear staining of TTF-1 is crispier and much easier to interpret than Napsin-A cytoplasmic stain. An antibody panel including TTF-1 and Napsin-A or a dual stain will be very helpful in determining the origin of metastatic adenocarcinoma in serous effusion.

New immunohistochemical markers in the differential diagnosisof nonsmall cell lung carcinoma.

BACKGROUND/AIM: The aim of this study was to investigate Napsin-A, NTRK-1, NTRK-2, Desmoglein-3, and Desmocollin-3 in the differential diagnosis and prognosis of nonsmall cell lung cancer. MATERIALS AND METHODS: The expression of Napsin-A, NTRK-1, NTRK-2, and Desmoglein-3 was examined by immunohistochemistry in 50 squamous cell carcinomas and 50 adenocarcinomas. Desmocollin-3 was investigated in 29 squamous cell carcinoma and 29 adenocarcinoma cases. Associations between expression profiles of Napsin-A, NTRK-1, NTRK-2, Desmoglein-3, and Desmocollin-3 in lung cancers and clinicopathological variables were analyzed. RESULTS: Napsin-A staining was statistically significant in detecting adenocarcinomas versus squamous cell carcinomas. The sensitivity of Napsin-A for adenocarcinomas was 96% and the specificity was 100%. NTRK-2 and Desmocollin-3 staining were statistically significant in detecting squamous cell carcinomas versus adenocarcinomas. Desmoglein-3, Napsin-A, and NTRK-2 had no effect on survival. Disease-free survival time was significantly shorter in cases that were moderately positive with NTRK-1. CONCLUSION: Our data suggest that Napsin-A, NTRK-2, and Desmocollin-3 are useful markers in the differentiation of nonsmall cell lung cancer.

Prognostic implications of immunohistochemistry markers for EGFR-TKI therapy in Chinese patients with advanced lung adenocarcinoma harboring EGFR mutations.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutations in non-small-cell lung cancer predict dramatic clinical responses to tyrosine kinase inhibitor (TKI) treatment. The conclusion on EGFR mutation-specific antibodies by immunohistochemistry (IHC) is not consistent. We evaluated the clinical availability of EGFR mutation-specific antibodies, investigating the prediction role of mutant EGFRs and other IHC markers in TKI therapy in patients with advanced lung adenocarcinoma. MATERIALS AND METHODS: We analyzed 637 primary lung adenocarcinomas from an unselected Chinese population. For IHC, antibodies against EGFR exon 19 E746_A750 deletions, exon 21 L858R mutations, thyroid transcription factor-1 (TTF-1), and Napsin-A were applied. Positivity was defined as staining score >0. RESULTS: Specificities of E746_A750 and L858R antibodies were 99.6% and 99.3%, while sensitivities were 86.0% and 82.7%, respectively. Tumors with Napsin-A positivity, TTF-1 positivity, EGFR mutations, and lepidic pattern showed a lower marker of proliferation index (Ki67). Higher expression scores of mutant EGFR protein, TTF-1 positivity, lower Ki67 proliferation index, and lepidic pattern were associated with longer progression-free survival. CONCLUSION: High scores of mutant EGFR, Napsin-A positivity, TTF-1 positivity, lower Ki67 index, and lepidic pattern were favorable predictors for TKI therapy in patients with advanced lung adenocarcinoma.

Gastric metastasis from primary lung adenocarcinoma mimicking primary gastric cancer.

Gastric metastases from lung adenocarcinoma are rare. Because gastric metastasis grossly resembles advanced gastric cancer, it is difficult to diagnose gastric metastasis especially when the histology of the primary lung cancer is adenocarcinoma. We describe a case of gastric metastasis from primary lung adenocarcinoma mimicking Borrmann type IV primary gastric cancer. A 68-year-old man with known lung adenocarcinoma with multiple bone metastases had been experiencing progressive epigastric pain and dyspepsia over one year. Esophagogastroduodenoscopy revealed linitis plastica-like lesions in the fundus of the stomach. Pathologic examination revealed a moderately differentiated adenocarcinoma with submucosal infiltration. Positive immunohistochemical staining for thyroid transcription factor-1 (TTF-1) and napsin A (Nap-A) confirmed that the metastasis was pulmonary in origin. The patient had been treated with palliative chemotherapy for the lung cancer and had lived for over fifteen months after the diagnosis of gastric metastasis. Clinicians should be aware of the possibility of gastric metastasis in patients with primary lung adenocarcinoma, and additional immunohistochemical staining for Nap-A as well as TTF-1 may help in differentiating its origin.

Expression and clinical significance of CK5/6, DSG3, P40, TTF-1, CK7, NapsinA in small biopsy specimens of non-small cell lung cancer / 中国基层医药

Objective@#To detect the expression and the differential significance of CK5/6, DSG3, P40, TTF-1, CK7, NapsinA in small biopsy specimens of non-small cell lung cancer (NSCLC), squamous cell carcinoma (SCC) and adenocarcinoma (AC).@*Methods@#Immunohistochemical SP method was used to detect the expressions of CK5/6, DSG3, P40, TTF-1, CK7 and NapsinA in 120 small biopsy specimens of NSCLC hospitalized in the Central People's Hospital of Tengzhou from January 2016 to December 2017, and the results were analyzed combined with the clinical characteristics of NSCLC.@*Results@#The positive expression rates of CK5/6, DSG3 and P40 in lung SCC were 100.0%(56/56), 89.3%(50/56) and 96.4%(54/56), respectively, with specificity of 90.6%, 100.0% and 100.0%, respectively.The positive expression rates of NapsinA, TTF-1 and CK7 in lung AC were 81.3%(52/64), 90.6%(58/64) and 93.8%(60/64), respectively, with specificity of 100.0%, 92.9% and 96.4%, respectively.The positive expression rates of CK5/6, DSG3, P40 in SCC had statistically significant differences compared with those in AC (all P<0.05), and the expression of TTF-1, CK7 and NapsinA in AC had statistically significant differences compared with those in SCC (all P<0.05).@*Conclusion@#CK5/6, DSG3, P40, TTF-1, CK7 and NapsinA are of great significance in the differential diagnosis of SCC and AC in small biopsy specimens of NSCLC.

Expression and clinical significance of CK5／6,DSG3,P40,TTF-1,CK7,NapsinA in small biopsy specimens of non-small cell lung cancer / 中国基层医药

Objective To detect the expression and the differential significance of CK 5／6,DSG3,P40,TTF-1,CK7,NapsinA in small biopsy specimens of non -small cell lung cancer ( NSCLC),squamous cell carcinoma (SCC) and adenocarcinoma (AC).Methods Immunohistochemical SP method was used to detect the expressions of CK5／6,DSG3,P40,TTF-1,CK7 and NapsinA in 120 small biopsy specimens of NSCLC hospitalized in the Central People's Hospital of Tengzhou from January 2016 to December 2017,and the results were analyzed combined with the clinical characteristics of NSCLC.Results The positive expression rates of CK5／6,DSG3 and P40 in lung SCC were 100.0%(56／56),89.3%(50／56) and 96.4%(54／56), respectively,with specificity of 90.6%,100.0% and 100.0%,respectively.The positive expression rates of NapsinA ,TTF-1 and CK7 in lung AC were 81.3%(52／64), 90.6%(58／64) and 93.8%(60／64),respectively,with specificity of 100.0%,92.9% and 96.4%,respectively. The positive expression rates of CK5／6,DSG3,P40 in SCC had statistically significant differences compared with those in AC (all P＜0.05),and the expression of TTF -1,CK7 and NapsinA in AC had statistically significant differences compared with those in SCC ( all P＜0.05).Conclusion CK5／6,DSG3,P40,TTF-1,CK7 and NapsinA are of great significance in the differential diagnosis of SCC and AC in small biopsy specimens of NSCLC .

Napsin-A, TTF-1, EGFR, and ALK Status Determination in Lung Primary and Metastatic Mucin-Producing Adenocarcinomas.

Pulmonary mucin-producing adenocarcinomas may be indistinguishable on conventional histology from a metastasis, as thyroid transcription factor-1 (TTF-1) expression often is lacking and KRAS mutations are widely present even in extrapulmonary sites. Few data have been reported on the diagnostic role of napsin-A and epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) gene alterations in this challenging differential diagnosis. Seventy-seven surgically resected cases, including 53 primary and 24 metastatic tumors from different sites, were evaluated for napsin-A, TTF-1, and ALK by immunohistochemistry and for EGFR mutations by direct sequencing. Overall, napsin-A expression in primary lung mucin-producing adenocarcinomas was 36% (8% mucinous, 17% colloid, 87.5% solid, and 100% signet ring cell) and TTF-1 expression reached an overall figure of 42% (12.5% mucinous, 33% colloid, 87.5% solid, and 100% signet ring cell). Metastatic mucinous adenocarcinomas did not react with napsin-A or with TTF-1. All primary and metastatic tumors lacked EGFR mutations, while a single case of signet ring cell lung adenocarcinoma showed ALK expression and rearrangement at fluorescent in situ hybridization analysis. Napsin-A has a lower sensitivity compared with TTF-1 in primary mucin-producing adenocarcinomas of the lung. However, both antibodies have an absolute specificity, being always negative in metastatic mucinous adenocarcinomas. EGFR mutations and ALK translocation or expression are exceedingly rare in mucin-producing adenocarcinomas of the lung, resulting unnecessary as diagnostic tool in this setting.