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Objective:To evaluate the value of p16 INK4a detected by p16 INK4a immunostaining as a new generation of cervical cytology for primary screening and secondary screening in population-based cervical cancer screening, and in improving cytological diagnosis. Methods:Between 2016 and 2018, 5 747 non-pregnant women aged 25-65 years with sexual history were recruited and underwent cervical cancer screening via high-risk (HR)-HPV/liquid-based cytological test (LCT) test in Shenzhen and surrounding areas. All slides were immuno-stained using p16 INK4a technology, among them, 902 cases were offered p16 INK4a detection during primary screening, and the remaining 4 845 cases were called-back by the virtue of abnormal HR-HPV and LCT results for p16 INK4a staining. Participants with complete LCT examination, HR-HPV test, p16 INK4a staining and histopathological examination results were included in this study. The performance of p16 INK4a in primary and secondary screening, and in assisting cytology to detect high grade squamous intraepithelial lesion [HSIL, including cervical intraepithelial neoplasia (CIN) Ⅱ or Ⅲ] or worse [HSIL (CIN Ⅱ) + or HSIL (CIN Ⅲ) +] were analyzed. Results:(1) One-thousand and ninety-seven cases with complete data of p16 INK4a and histology were included. Pathological diagnosis: 995 cases of normal cervix, 37 cases of low grade squamous intraepithelial lesion (LSIL), 64 cases of HSIL and one case of cervical cancer were found. Among them, 65 cases of HSIL (CIN Ⅱ) + and 34 cases of HSIL (CIN Ⅲ) + were detected. The positive rate of p16 INK4a in HSIL (CIN Ⅱ) + was higher than that in CINⅠ or normal pathology (89.2% vs 10.2%; P<0.01). (2) p16 INK4a as primary screening for HSIL (CIN Ⅱ) + or HSIL (CIN Ⅲ) + was equally sensitive to primary HR-HPV screening (89.2% vs 95.4%, 94.1% vs 94.1%; P>0.05), but more specific than HR-HPV screening (89.8% vs 82.5%, 87.7% vs 80.2%; P<0.05). p16 INK4a was equally sensitive and similarly specific to cytology (≥LSIL; P>0.05). (3) The specificity of LCT adjunctive p16 INK4a for detecting HSIL (CIN Ⅱ) + or HSIL (CIN Ⅲ) + were higher than that of LCT alone or adjunctive HR-HPV ( P<0.01), while the sensitivity were similar ( P>0.05). (4) p16 INK4a staining as secondary screening: p16 INK4a was significantly more specific (94.1% vs 89.7%, 91.9% vs 87.4%; P<0.01) and comparably sensitive (84.6% vs 90.8%, 88.2% vs 91.2%; P>0.05) to cytology for triaging primary HR-HPV screening. HPV 16/18 to colposcopy and triage other HR-HPV with p16 INK4a was equally sensitive (88.2% vs 94.1%; P=0.500) and more specific (88.3% vs 83.0%; P<0.01) than HPV 16/18 to colposcopy and triage other HR-HPV with LCT≥ atypical squamous cells of undetermined significance (ASCUS), and the referral rate decreased (14.0% vs 19.4%; P=0.005). Conclusions:For primary screening, p16 INK4a is equally specific to cytology and equally sensitive to HR-HPV screening. p16 INK4a alone could be an efficient triage after primary HR-HPV screening. In addition, p16 INK4a immunostaining could be used as an ancillary tool to cervical cytological diagnosis, and improves its accuracy in cervical cancer screening.
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Objective To evaluate recurrence risk factors in postoperative breast cancer patients after 5-year adjuvant endocrine therapy.Methods From Jan 2006 to Dec 2011,a total of 327 patients were enrolled for this study.Kaplan-Meier curves were applied to estimate survival rates and COX's proportional hazards model to identify prognostic variables.Results Among these 327 eligible patients,42 (12.8％) patients suffered from distant metastasis and 34 (10.4％) patients experienced locoregional recurrence after 5-year adjuvant endocrine therapy.Survival analysis showed that patients with histologic grade 3 disease,lymph node metastasis,Ki-67 high expression,high TNM stage and radiotherapy were statistically significant with poorer relapse-free survival (RFS,P =0.000,0.003,0.000,0.003,0.034)and poorer distant metastasis-free survival (DMFS,P =0.000,0.002,0.000,0.002,0.023),respectively.In multivariate analysis,patients with histological grade 3 disease (P =0.002) and more than 3 positive nodes (P =0.032) were risk factors for lower RFS.However,only histological grade 3 (P =0.015) was risk factor for DMFS.Conclusions Late relapse after completion of 5-year adjuvant endocrine therapy was still common,patients with grade 3 disease and more than 3 positive nodes may benefit from extended endocrine therapy.
ABSTRACT
Endocrine therapy is an important treatment of estrogen receptor (ER) positive breast cancer.However,late relapse after completion of 5-year adjuvant endocrine therapy is still common.Extended endocrine therapy (EET) is a promising strategy to further reduce the risk of recurrence and increase the cure rate in early-stage patients.The decision-making to EET should be individually implemented by weighing the risk of late recurrence,menopausal status,side effects,and patients' preference.Future studies are still needed to identify the patients who are most likely to benefit from EET.
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Objective To investigate the correlations between P53 expression and clinicopathologic factors and prognosis of Luminal breast cancer.Methods From January 2009 to December 2012,a total of 283 patients with Luminal breast cancer in the Shanghai General Hospital Affiliated to Shanghai Jiaotong Univer-sity were included.P53 expressions of them were assayed by immunohistochemistry.Survival analysis was applied using Kaplan-Meier curve and Log-rank test.Single factor analysis and mutiple-factor analysis were applied using Cox proportional hazard regression model.Results The rate of P53 expression was associated with tumor size (χ2 =6.285,P =0.043),lymph node metastasis (χ2 =15.881,P =0.000),histological grade (χ2 =8.132,P =0.043)and Ki-67 (χ2 =6.476,P =0.039),but it was not associated with age (χ2 =0.955,P =0.328),menopausal status (χ2 =3.808,P =0.051),pathological pattern (χ2 =0.847,P =0.655),estrogen receptor (χ2 =1.867,P =0.172),progesterone receptor (χ2 =0.937,P =0.333)and human epidermal growth factor receptor-2 (χ2 =0.110,P =0.741 ).In all the 283 patients,the 5-year relapse-free survival rates for P53-positive group and P53-negative group were 66.7% and 90.7% respectively (χ2 =12.609,P =0.000),while the 5-year overall survival rates were 84.4% and 93.4% respectively (χ2 =4.153,P =0.042),with significant differences.In Cox mutiple-factor analysis,lymph node metastasis (HR =2.484,95%CI:1.393-4.431,χ2 =9.497,P =0.002)and P53 over-expression (HR =3.627,95%CI:1.061-12.401,χ2 =4.220,P =0.040)were independent prognostic factors for the relapse-free survival of patients with Luminal breast cancer,and lymph node metastasis (HR =3.451,95%CI:1.891-6.297,χ2 =16.290,P =0.000)and higher histological grade (HR =2.806,95%CI:1.091-7.219,χ2 =4.582,P =0.032)were independent prognostic factors for overall survival.Conclusion P53 over-expression of patients with Luminal breast cancer is associated with prognostic factors such as lymph node metastasis and histological grade,which indicates the worse prognosis.
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Papillary thyroid cancer (PTC) is the most common malignant neoplasm originating from the thyroid gland and has an excellent prognosis.But cervical lymph node metastases are common and the most common sites of metastases are the central lymph nodes of the neck (level Ⅵ).While therapeutic central lymph node dissection for involved lymph nodes is needed in our nation and others,the controversial topic is whether routine prophylactic central lymph node dissection in patients without evidence of lymph node metastasis should be performed in patients with PTC.The author reviewed the research development of prophylactic central lymph node dissection for papillary thyroid cancer in the article.
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Ki-67 is a common proliferation marker,especially used to reflect the proliferation activity of malignancy cells.Recently this marker has been widely studied among early breast cancer patients,However,to date,whether include Ki67 in the list of required routine biological markers there is still a hot argument.This review mainly explores and summarizes the prognostic and predictive role of this marker in breast cancer,the clinical value of the combination of Ki-67 and other makers,and the problems lie in the application of Ki-67 in clinical practice.