Expressions of serum N-terminal osteocalcin and cytokeratin 5/6 in primary lung cancer patients with bone metastasis and their clinical significances / 肿瘤研究与临床

Objective:To explore the expressions of serum N-terminal osteocalcin (N-MID) and cytokeratin (CK) 5/6 in primary lung cancer patients with bone metastasis and their clinical significances.Methods:The clinical data of 96 patients with primary lung cancer admitted to Chengdu Second People's Hospital between February 2019 to February 2022 were retrospectively analyzed. All patients were divided into the bone metastasis group (38 cases) and the non-bone metastasis group (58 cases) according to whether bone metastasis occurred, and 45 healthy people who underwent physical examination during the same period were treated as the healthy control group. The expression levels of serum N-MID and CK5/6 in the bone metastasis group, the non-bone metastasis group and the healthy control group were compared. Logistic regression was used to analyze the factors affecting bone metastasis in patients with primary lung cancer; receiver operating characteristic (ROC) curve analysis was used to analyze the value of the expression levels of serum N-MID and CK5/6 in predicting bone metastasis in patients with primary lung cancer.Results:The composition ratio of patients with pathological stage Ⅲ-Ⅳ, serum bone-derived alkaline phosphatase and N-MID expression levels in the bone metastasis group were higher than those in the non-bone metastasis group (all P < 0.05). The expression level of serum N-MID in the bone metastasis group and non-bone metastasis group was higher than that in the healthy control group [(26.0±5.3) ng/ml, (15.3±3.1) ng/ml vs. (9.9±1.7) ng/ml, F = 224.27, P < 0.001], and there were statistically significant differences in the serum N-MID expression level of the pairwise comparison among the three groups (all P < 0.05). The expression level of serum CK5/6 in the bone metastasis group and the non-bone metastasis group was lower than that in the healthy control group [(3.6±0.7) ng/ml, (7.3±1.4) ng/ml vs. (10.6±2.4) ng/ml, F = 178.11, P < 0.001], and there were statistically significant differences in the serum CK5/6 expression level of the pairwise comparison among the three groups (all P < 0.05). Multivariate analysis showed that CK5/6, N-MID and bone-derived alkaline phosphatase were independent affecting factors for bone metastasis in patients with primary lung cancer ( OR = 4.088, 3.615, 2.892, all P < 0.05). ROC curve analysis showed that the optimal cut-off values of serum N-MID and CK5/6 expression levels for predicting bone metastasis in patients with primary lung cancer were 18.59 ng/ml and 4.71 ng/ml; the corresponding the area under the curve (AUC) was 0.881 and 0.862, respectively; and the specificity and AUC of the combination of serum N-MID and CK5/6 in predicting the bone metastasis in patients with primary lung cancer was 98.28% and 0.937 (95% CI 0.869-0.977), respectively; the AUC predicted by the combination of both was higher than that by serum N-MID or CK5/6 single (all P < 0.001). Conclusions:The expression levels of serum N-MID and CK5/6 in primary lung cancer patients with bone metastasis are abnormally changed. Clinical detection of serum N-MID and CK5/6 expression levels may be used as sensitive indicators for predicting the bone metastasis in patients with primary lung cancer.

Prognosis of breast cancer with low-positive hormonal receptors using epidermal growth factor receptor and cytokeratin 5/6 as indi-cators / 中华内分泌外科杂志

Objective Less than a decade ago, ER-positive and PgR-positive diagnostic criteria decrease from 10%to 1%. Up to 20%of current immunohistochemical determinations of ER and PgR worldwide may be inaccu-rate. It is necessary to study patients whose tumors are between luminal A (LABC) and triple-negative (TNBC) breast cancer. Methods Survival analysis grouping by the level of positive hormone receptor, CK5/6 and EGFR, and en-docrine therapy was carried out in 206 patients whose tumors were junction zone between LABC and TNBC. Re-sults There were no significant differences between the low-positive (1%-9%) HR group and positive HR (10%-19%) group in overall survival (OS) and disease-free survival (DFS). There was an apparent difference between the nor-mal-like group and basal-like group in OS and DFS, and between the patients with and without endocrine therapy. There were significant differences between death and tumor progression for EGFR and CK5/6, chemotherapy, and endocrine therapy. Conclusions We conclude that EGFR and CK5/6 are better prognostic indicators than the lev-el of positive HR in patients whose tumors are junction zone at the junction zone between LABC and TNBC. En-docrine therapy can be highly beneficial to these patients regardless of the positive HR level.

Molecular phenotypes of ductal carcinoma-in-situ and invasive ductal carcinoma: A comparative study.

Aims and Objectives: This study was aimed at analyzing the prevalence of molecular phenotypes in invasive ductal carcinoma (IDC) and coexisting ductal carcinoma-in-situ (DCIS) and to correlate with clinicopathological features. Materials and Methods: In this study, 75 cases of IDC with coexisting DCIS were included. Molecular phenotype was determined using expression of estrogen receptor, progesterone receptor, HER2/neu, and cytokeratin 5/6. Statistical analysis was performed for correlation between molecular phenotypes and clinicopathologic parameters. Results: Of the 75 cases, the invasive component in all cases was IDC-not otherwise specified. About one-third of our patients were post-menopausal. The most common molecular phenotype was luminal A (45.3%) followed by HER2-expressing type (24%). In all cases, the molecular phenotype was identical in DCIS and the invasive component. HER2-expressing tumors were found to be larger in size with frequent nodal involvement. On statistical analysis, tumor size and grade were found to correlate with the molecular phenotype. Conclusion: In conclusion, the molecular phenotype in DCIS correlates well with that of coexisting IDC, suggesting that DCIS is a precursor lesion in these tumors. This correlation of molecular phenotype can be utilized in prediction of phenotype of the invasive component in a case with in-situ carcinoma.

Cytokeratin 5/6 expression in benign and malignant breast lesions.

Background: Cytokeratin s (CK) are used for the fingerprinting of carcinomas in general. In breast tissue, the luminal epithelial cells express CK 8/18, CK 7 and CK 19, while basal/myoepithelial cells express CK 5/6, CK 14 and CK 17. Material and Methods: Immunohistochemical staining for cytokeratin 5/6 was applied on cell block sections of 23 cases of benign and 25 cases of malignant breast lesions using avidin biotin peroxidase technique. The distribution and intensity of staining was recorded and graded semiquantitatively. Result: All benign lesions showed positive immunoreaction, with the staining index varying from 6-9, except lactating adenoma. The malignant lesions comprised three cases of ductal carcinoma in situ (DCIS) and 22 cases of infiltrating ductal carcinoma, not otherwise specified, IDC (NOS). None of the DCIS cases showed a positive immunoreaction. Among the IDC (NOS) lesions, six cases of grade III breast carcinoma exhibited a positive immunohistochemical reaction, the staining index of which varied from 2-6. The staining reaction in the malignant lesions was only cytoplasmic and the intensity was significantly less than that of benign lesions. Conclusion: CK 5/6 expression breast carcinoma implies a 'basal like' molecular phenotype and is associated with poor prognosis. This antibody is also used as a component of panels to differentiate benign and malignant breast lesions.