Objective: To investigate the diagnostic efficiency of conventional serum tumor markers and their combination with chest CT for stage ⅠA lung cancer. Methods: A total of 1 155 patients with stage ⅠA lung cancer and 200 patients with benign lung lesions (confirmed by surgery) treated at the Cancer Hospital, Chinese Academy of Medical Sciences from January 2016 to October 2020 were retrospectively enrolled in this study. Six conventional serum tumor markers [carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), squamous cell carcinoma associated antigen (SCCA), cytokeratin 19 fragment (CYFRA21-1), neuron-specific enolase (NSE), and gastrin-releasing peptide precursor (ProGRP)] and chest thin-slice CT were performed on all patients one month before surgery. Pathology was taken as the gold standard to analyze the difference of positivity rates of tumor markers between the lung cancer group and the benign group, the moderate/poor differentiation group and the well differentiation group, the adenocarcinoma group and the squamous cell carcinoma group, the lepidic and non-lepidic predominant adenocarcinoma groups, the solid nodule group and the subsolid nodule group based on thin-slice CT, and subgroups of ⅠA1 to ⅠA3 lung cancers. The diagnostic performance of tumor markers and tumor markers combined with chest CT was analyzed using the receiver operating characteristic curve. Results: The positivity rates of six serum tumor markers in the lung cancer group and the benign group were 2.32%-20.08% and 0-13.64%, respectively; only the SCCA positivity rate in the lung cancer group was higher than that in the benign group (10.81% and 0, P=0.022). There were no significant differences in the positivity rates of other serum tumor markers between the two groups (all P>0.05). The combined detection of six tumor markers showed that the positivity rate of the lung cancer group was higher than that of the benign group (40.93% and 18.18%, P=0.004), and the positivity rate of the adenocarcinoma group was lower than that of the squamous cell carcinoma group (35.66% and 47.41%, P=0.045). The positivity rates in the poorly differentiated group and moderately differentiated group were higher than that in the well differentiated group (46.48%, 43.75% and 22.73%, P=0.025). The positivity rate in the non-lepidic adenocarcinoma group was higher than that in lepidic adenocarcinoma group (39.51% and 21.74%, P=0.001). The positivity rate of subsolid nodules was lower than that of solid nodules (30.01% vs 58.71%, P=0.038), and the positivity rates of stageⅠA1, ⅠA2 and ⅠA3 lung cancers were 33.33%, 48.96% and 69.23%, respectively, showing an increasing trend (P=0.005). The sensitivity and specificity of the combined detection of six tumor markers in the diagnosis of stage ⅠA lung cancer were 74.00% and 56.30%, respectively, and the area under the curve (AUC) was 0.541. The sensitivity and specificity of the combined detection of six serum tumor markers with CT in the diagnosis of stage ⅠA lung cancer were 83.0% and 78.3%, respectively, and the AUC was 0.721. Conclusions: For stage ⅠA lung cancer, the positivity rates of commonly used clinical tumor markers are generally low. The combined detection of six markers can increase the positivity rate. The positivity rate of markers tends to be higher in poorly differentiated lung cancer, squamous cell carcinoma, or solid nodules. Tumor markers combined with thin-slice CT showed limited improvement in diagnostic efficiency for early lung cancer.
Humans ; Lung Neoplasms/diagnostic imaging* ; Biomarkers, Tumor ; Retrospective Studies ; Antigens, Neoplasm ; Keratin-19 ; Carcinoembryonic Antigen ; Adenocarcinoma/diagnostic imaging* ; Carcinoma, Squamous Cell/diagnostic imaging* ; Phosphopyruvate Hydratase ; Tomography, X-Ray Computed

Objective: To investigate the diagnostic efficiency of conventional serum tumor markers and their combination with chest CT for stage ⅠA lung cancer. Methods: A total of 1 155 patients with stage ⅠA lung cancer and 200 patients with benign lung lesions (confirmed by surgery) treated at the Cancer Hospital, Chinese Academy of Medical Sciences from January 2016 to October 2020 were retrospectively enrolled in this study. Six conventional serum tumor markers [carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), squamous cell carcinoma associated antigen (SCCA), cytokeratin 19 fragment (CYFRA21-1), neuron-specific enolase (NSE), and gastrin-releasing peptide precursor (ProGRP)] and chest thin-slice CT were performed on all patients one month before surgery. Pathology was taken as the gold standard to analyze the difference of positivity rates of tumor markers between the lung cancer group and the benign group, the moderate/poor differentiation group and the well differentiation group, the adenocarcinoma group and the squamous cell carcinoma group, the lepidic and non-lepidic predominant adenocarcinoma groups, the solid nodule group and the subsolid nodule group based on thin-slice CT, and subgroups of ⅠA1 to ⅠA3 lung cancers. The diagnostic performance of tumor markers and tumor markers combined with chest CT was analyzed using the receiver operating characteristic curve. Results: The positivity rates of six serum tumor markers in the lung cancer group and the benign group were 2.32%-20.08% and 0-13.64%, respectively; only the SCCA positivity rate in the lung cancer group was higher than that in the benign group (10.81% and 0, P=0.022). There were no significant differences in the positivity rates of other serum tumor markers between the two groups (all P>0.05). The combined detection of six tumor markers showed that the positivity rate of the lung cancer group was higher than that of the benign group (40.93% and 18.18%, P=0.004), and the positivity rate of the adenocarcinoma group was lower than that of the squamous cell carcinoma group (35.66% and 47.41%, P=0.045). The positivity rates in the poorly differentiated group and moderately differentiated group were higher than that in the well differentiated group (46.48%, 43.75% and 22.73%, P=0.025). The positivity rate in the non-lepidic adenocarcinoma group was higher than that in lepidic adenocarcinoma group (39.51% and 21.74%, P=0.001). The positivity rate of subsolid nodules was lower than that of solid nodules (30.01% vs 58.71%, P=0.038), and the positivity rates of stageⅠA1, ⅠA2 and ⅠA3 lung cancers were 33.33%, 48.96% and 69.23%, respectively, showing an increasing trend (P=0.005). The sensitivity and specificity of the combined detection of six tumor markers in the diagnosis of stage ⅠA lung cancer were 74.00% and 56.30%, respectively, and the area under the curve (AUC) was 0.541. The sensitivity and specificity of the combined detection of six serum tumor markers with CT in the diagnosis of stage ⅠA lung cancer were 83.0% and 78.3%, respectively, and the AUC was 0.721. Conclusions: For stage ⅠA lung cancer, the positivity rates of commonly used clinical tumor markers are generally low. The combined detection of six markers can increase the positivity rate. The positivity rate of markers tends to be higher in poorly differentiated lung cancer, squamous cell carcinoma, or solid nodules. Tumor markers combined with thin-slice CT showed limited improvement in diagnostic efficiency for early lung cancer.
Humans ; Lung Neoplasms/diagnostic imaging* ; Biomarkers, Tumor ; Retrospective Studies ; Antigens, Neoplasm ; Keratin-19 ; Carcinoembryonic Antigen ; Adenocarcinoma/diagnostic imaging* ; Carcinoma, Squamous Cell/diagnostic imaging* ; Phosphopyruvate Hydratase ; Tomography, X-Ray Computed

Patients with lung cancer at the same stage may have markedly different overall outcome and a lack of specific biomarker to predict lung cancer outcome. Heat-shock protein 90 β (HSP90β) is overexpressed in various tumor cells. In this study, the ELISA results of HSP90β combined with CEA, CA125, and CYFRA21-1 were used to construct a recursive partitioning decision tree model to establish a four-protein diagnostic model and predict the survival of patients with lung cancer. Survival analysis showed that the recursive partitioning decision tree could distinguish the prognosis between high- and low-risk groups. Results suggested that the joint detection of HSP90β, CEA, CA125, and CYFRA21-1 in the peripheral blood of patients with lung cancer is plausible for early diagnosis and prognosis prediction of lung cancer.
Antigens, Neoplasm ; Biomarkers, Tumor ; CA-125 Antigen ; Carcinoembryonic Antigen ; Carcinoma, Non-Small-Cell Lung/pathology* ; Humans ; Keratin-19 ; Lung Neoplasms ; Prognosis

OBJECTIVE: To evaluate the diagnostic value of the serum tumor markers carcinoembryonic antigen (CEA), cytokeratin-19-fragment (CYFRA21-1), squamous cell carcinoma associated antigen (SCCAg), neuron-specificenolase (NSE) and pro-gastrin-releasing peptide (ProGRP) for lung cancers of different pathological types. METHODS: This study was conducted among patients with established diagnoses of lung adenocarcinoma (LADC, n=137), lung squamous cell carcinoma (LSCC, n=82), small cell lung carcinoma (SCLC, n=59), and benign chest disease (BCD, n=102). The serum tumor markers were detected for all the patients for comparison of the positivity rates and their serum levels. ROC curve was used for analysis of the diagnostic efficacy of these tumor markers either alone or in different combinations. RESULTS: In patients with LADC, the positivity rate and serum level of CEA were significantly higher than those in the other groups (P < 0.05); the patients with LSCC had the highest positivity rate and serum level of SCCAg among the 4 groups (P < 0.05). The positivity rates and serum levels of ProGRP and NSE were significantly higher in SCLC group than in the other groups (P < 0.05). CYFRA21-1 showed the highest positivity rate and serum level in LADC group and LSCC group. With the patients with BCD as control, CEA showed a diagnostic sensitivity of 62.8% and a specificity of 93.1% for LADC, and the sensitivity and specificity of SCCAg for diagnosing LSCC were 64.6% and 91.2%, respectively. CYFRA21-1 had the highest diagnostic sensitivity for LADC and LSCC. The diagnostic sensitivity and specificity of ProGRP for SCLC were 83.1% and 98.0%, respectively. When combined, CYFRA21-1 and CEA showed a high sensitivity (78.8%) and specificity (86.3%) for diagnosing LADC with an AUC of 0.891; CYFRA21-1 and SCCAg had a high sensitivity (84.1%) and specificity (87.3%) for diagnosing LSCC with an AUC of 0.912. NSE combined with ProGRP was highly sensitive (88.1%) and specific (98.0%) for diagnosis of SCLC, with an AUC of 0.952. For lung cancers of different pathological types, the combination of all the 5 tumor markers showed no significant differences in the diagnostic power from a combined detection with any two of the markers (P>0.05). CONCLUSION CEA, CYFRA21-1, SCCAg, NSE and ProGRP are all related to the pathological type of lung cancers and can be used in different combinations as useful diagnostic indicators for lung cancers.
Antigens, Neoplasm ; Biomarkers, Tumor ; Carcinoembryonic Antigen ; Humans ; Keratin-19 ; Lung Neoplasms/pathology* ; Peptide Fragments ; Peptide Hormones ; Recombinant Proteins ; Small Cell Lung Carcinoma/diagnosis*

A 41-year-old female patient was admitted in Department of Respiratory and Critical Care Medicine, Peking University Third Hospital because of having cough for a year. Multiple subpleural ground grass and solid nodules could be seen on her CT scan. Four months before admission, she began to experience dry mouth and eyes, blurred vision, finger joints pain, muscle pain and weakness in both lower limbs and weight loss. At the time of admission, the patient's vital signs were normal, no skin rash was seen, breath sounds in both lungs were clear, no rales or wheeze, no deformities in her hands, no redness, swelling, or tenderness in the joints. There was no edema in both lower limbs. Some lab examinations were performed. Tumor markers including squamous cell carcinoma (SCC) antigen, neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), Cyfra21-1, pro-gastrin-releasing peptide (proGRP), carbohydrate antigen 125 (CA125) and carbohydrate antigen 199 (CA199) were all normal. The antinuclear antibody, rheumatoid factor, antineutrophil cytoplasmic antibody, anti-dsDNA antibody, anti-Sm antibody, anti-SSA/SSB antibody, anti-ribonucleoprotein (RNP) antibody, anti-Jo-1 antibody, anti-SCL-70 antibody and anti-ribosomal antibody were all negative. The blood IgG level was normal. The blood fungal β-1.3-D glucose, aspergillus galactomannan antigen, sputum bacterial and fungal culture, and sputum smear test for acid-fast staining were all negative. Lung function was normal. Bronchoscopy showed the airways and mucosa were normal. To clarify the diagnosis, she underwent thoracoscopic lung biopsy, the histopathology revealed follicular bronchiolitis (FB) with nonspecific interstitial pneumonia (NSIP). She did not receive any treatment and after 7 months, the lung opacities were spontaneously resolved. After 7 years of follow-up, the opacities in her lung did not relapse. To improve the understanding of FB, a literature research was performed with "follicular bronchiolitis" as the key word in Wanfang, PubMed and Ovid Database. The time interval was from January 2000 to December 2018. Relative articles were retrieved and clinical treatments and prognosis of FB were analyzed. Eighteen articles concerning FB with complete records were included in the literature review. A total of 51 adult patients with FB were reported, including 18 primary FB and 33 secondary FB, and autoimmune disease was the most common underlying cause. Forty-one (80.4%) patients were prescribed with corticosteroids and/or immunosuppressive agents, 6 (11.8%) patients were treated with anti-infective, 5 (9.8%) patients did not receive any treatment. The longest follow-up period was 107 months. Among the 5 patients without any treatment, 1 patients died of metastatic melanoma, the lung opacities were unchanged in 1 patient and getting severe in 3 patients. In conclusion, FB is a rare disease, the treatment and prognosis are controversial. Corticosteroid and immunosuppressive agents could be effective. This case report suggests the possibility of spontaneous remission of FB.
Adult ; Antibodies, Antinuclear ; Antigens, Neoplasm ; Bronchiolitis ; Female ; Humans ; Keratin-19 ; Lung Diseases, Interstitial ; Remission, Spontaneous

19 fragment (CYFRA 21-1) and carcinoembryonic antigen (CEA) for the diagnosis of lung cancer and to establish the optimal cut-off values.METHODS: We retrospectively reviewed the medical records of 1,176 subjects with CYFRA 21-2 and CEA data; they were classified into 93 lung cancer cases and 1,083 total controls, including 146 age-matched controls. Multivariate analysis was used to determine the relationship between the concentration of each tumor marker and lung cancer diagnosis. The diagnostic efficiencies of tumor markers were evaluated using receiver operating characteristic curve analysis and areas under the curve (AUCs) were calculated. The optimal cut-offs for CYFRA 21-1 and CEA were also estimated.RESULTS: Age, CYFRA 21-1, and CEA concentrations were independently associated with lung cancer diagnosis. Diagnostic efficiency of each tumor marker and its' combination was different according to the histological types of lung cancer. For non-small cell lung cancer, the AUCs for the two-marker combination were the highest: 0.8661 and 0.7559 for total and age-matched controls, respectively. For squamous cell carcinoma, the AUCs for CYFRA 21-1 were the highest: 0.9245 and 0.8428 for total and age-matched controls, respectively. The sensitivity and specificity of CYFRA 21-1 and CEA for lung cancer diagnosis were improved when the cutoffs determined based on this study were applied.CONCLUSIONS: CYFRA 21-1 and CEA could be useful markers for diagnosing lung cancer and single or combination of markers may be useful according to different histological types of lung cancer.]]>
Area Under Curve ; Biomarkers, Tumor ; Carcinoembryonic Antigen ; Carcinoma, Non-Small-Cell Lung ; Carcinoma, Squamous Cell ; Diagnosis ; Keratin-19 ; Lung Neoplasms ; Lung ; Medical Records ; Multivariate Analysis ; Retrospective Studies ; ROC Curve ; Sensitivity and Specificity

BACKGROUND/AIMS: Lysyl oxidase-like 2 (LOXL2), a collagen-modifying enzyme, has been implicated in cancer invasiveness and metastasis. METHODS: We evaluated the expression of LOXL2 protein, in addition to carbonic anhydrase IX (CAIX), keratin 19, epithelial cell adhesion molecule, and interleukin 6, in 105 resected hepatocellular carcinomas (HCCs) by immunohistochemistry. RESULTS: LOXL2 positivity was found in 14.3% (15/105) of HCCs, and it was significantly associated with high serum α-fetoprotein levels, poor differentiation, fibrous stroma, portal vein invasion, and advanced TNM stage (p < 0.05 for all). Additionally, LOXL2 positivity was significantly associated with CAIX (p=0.005) and stromal interleukin 6 expression (p=0.001). Survival analysis of 99 HCC patients revealed LOXL2 positivity to be a poor prognostic factor; its prognostic impact appeared in progressed HCCs. Furthermore, LOXL2 positivity was shown to be an independent predictor of overall survival and disease-specific survival (p < 0.05 for all). Interestingly, co-expression of LOXL2 and CAIX was also an independent predictor for overall survival, disease-specific survival, disease-free survival, and extrahepatic recurrence-free survival (p < 0.05 for all). CONCLUSIONS: LOXL2 expression represents a subgroup of HCCs with more aggressive behavior and is suggested to be a poor prognostic marker in HCC patients.
Carbonic Anhydrases ; Carcinoma, Hepatocellular* ; Disease-Free Survival ; Epithelial Cells ; Extracellular Matrix ; Humans ; Immunohistochemistry ; Interleukin-6 ; Keratin-19 ; Neoplasm Metastasis ; Portal Vein ; Prognosis*

Hair follicle nevus (HFN) is a rare, benign, follicular hamartoma that most frequently presents as a congenital nodule on the face. We experienced a rare case of HFN on the neck of a 14-year-old boy and performed a pilot immunohistochemical study with cytokeratin 19 (CK19) to compare the staining pattern of hair follicles in HFN and its differential diagnoses, accessory tragus, cervical chondrocutaneous branchial remnants (CCBR) and trichofolliculoma. With hematoxylin and eosin stain, HFN showed numerous tiny hair follicles in the dermis with several sebaceous and eccrine glands, and perifollicular fibrous thickening. With CK19 stain, some hair follicles in HFN and CCBR showed positive expression, a few hair follicles in accessory tragus showed weak expression, and no hair follicles in trichofolliculoma showed expression. The present report supports the view that HFN, accessory tragus and CCBR are within the same spectrum of hamartomas.
Adolescent ; Dermis ; Diagnosis, Differential ; Eccrine Glands ; Eosine Yellowish-(YS) ; Hair Follicle ; Hair ; Hamartoma ; Hematoxylin ; Humans ; Keratin-19 ; Male ; Neck ; Nevus

Hepatoid carcinoma is extrahepatic neoplasm showing similar morphologic, immunohistochemical features with hepatocellular carcinoma. It's a very rare disease and has been reported most frequently in the stomach. Herein, we report a case of hepatoid carcinoma of pancreas presented with acute pancreatitis. The hepatoid carcinoma was diagnosed by his needle biopsy specimen and it showed pleomorphic nuclei and predominantly eosinophilic and occasionally clear cytoplasm in hematoxylin and eosin staining, and positive for HepPar-1 and cytokeratin 19 in immunohistochemical staining. Surgical treatment seems to be the best choice, if possible. However, there is no standard regimen for palliative chemotherapy. In our case, the patient was treated with 5-Fluorouracil (5-FU), folinic acid, irinotecan, oxaliplatin (FOLFIRINOX). The response was stable disease up to 4 month of follow up.
Biopsy, Needle ; Carcinoma, Hepatocellular ; Cytoplasm ; Drug Therapy ; Eosine Yellowish-(YS) ; Eosinophils ; Fluorouracil ; Follow-Up Studies ; Hematoxylin ; Humans ; Keratin-19 ; Leucovorin ; Pancreas* ; Pancreatitis* ; Rare Diseases ; Stomach

BACKGROUND: So far there's no tumor maker applied in diagnosis and treatment of thymic epithelial tumors. This study is to assess the correlation between serum cytokine 19 fragment (Cyfra 21-1) and clinicopathological features and prognosis of thymic epithelial tumors (TETs). METHODS: The clinical data of 159 patients with TETs in Shanghai Chest Hospital was retrospectively analysed. Patients were divided into groups according to different tumor stages and histotypes. Serum Cyfra 21-1 was thus compared. In addition, the possible relationship between perioperative serum Cyfra 21-1 level and the recurrent status was carrid out. RESULTS: Preoperative Cyfra 21-1 serum concentrations in patiants with advanced stage (T4) and thymic carcinomas were significantly higher than that in others (P<0.001, P<0.001, respectively). When the preoperative serum level exceeds the out-off of 1.66 ng/mL, it possibly indicates the recurrence during follow up. Furthermore, the sensitivity, specificity, and positive as well as negative predictive value (PPV and NPV) of postoperative Cyfra 21-1 to predict tumor recurrence were evaluated. At a cut-off of Cyfra 21-1 of 2.66 ng/mL, the sensitivity was 0.7, the specificity was 0.925, the PPV was 0.5 and the NPV was 0.966. CONCLUSIONS The elevated level of preoperative serum Cyfra 21-1 indicates an advanced stage of tumor or a more malignant histotype (thymic carcinoma). It also probably suggests a higher risk of tumor recurrence. During the oncological follow up, in addition to regular imaging examinations, the blood test of serum Cyfra 21-1 is also suggested to improve the diagnosis of tumor recurrence in order to improve the prognosis.
Biomarkers, Tumor ; blood ; Female ; Follow-Up Studies ; Humans ; Keratin-19 ; blood ; chemistry ; Male ; Middle Aged ; Neoplasms, Glandular and Epithelial ; blood ; diagnosis ; pathology ; Peptide Fragments ; blood ; Prognosis ; ROC Curve ; Retrospective Studies ; Thymus Neoplasms ; blood ; diagnosis ; pathology