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Immunosenescence is a process of immune dysfunction that occurs along with aging. Many studies have focused on the changes of different lymphocyte subsets in diseases and immune aging. However, the fluctuation in the number and phenotype of lymphocyte subset caused by aging have not been comprehensively analyzed, especially the effects of new indicators such as PD-1 and Ki67 in peripheral blood have been rarely reported. We further investigated the humoral and cellular immune parameters of 150 healthy donors over 18 years old. Age was associated with decreased CD4+CD45RA+CD62L+ T cells, decreased CD4+CD45RA+CD31+ T cells, and increased memory CD4+ or CD8+ T cells, dominated by male CD8+ T cells. The loss of CD28 expression on T cells and the transverse trend of activated CD38 and HLA-DR were also related to the increased age. In addition, CD8+ T cells in men were more prominent in activation indicators, and the difference between the old and young groups was obvious. CD4+CD25+CD127- T cells percentage tended to decrease with age and did not differ significantly between gender. Interestingly, we found that age was positively associated with PD-1+ T cells and showed significant age-related variability in men. Similarly, the percentage of CD8+ki-67+ also showed an increasing trend, with significant differences between the young group and other elderly groups in males. Our findings can provide immunological clues for future aging research, offering new insights for clinical monitoring and prevention of certain diseases.

The growing body of evidence suggests that breast cancer (BC) who achieve pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) may experience a more favorable prognosis. The objective of this study is to investigate the correlation between clinicopathologic parameters of locally advanced breast cancer (LABC) patients and the outcomes of NAC, with the aim of identifying predictive indicators for pCR. Additionally, we seek to examine the conversion of IHC markers in pCR patients following NAC and its impact on the prognosis of BC patients. We conducted a study involving 126 patients with LABC. Clinicopathological parameters associated with pCR were subjected to univariate and multivariate analysis. Kaplan-Meier (KM) curves and the log-rank test were used to compare the statistical difference in prognosis in different groups of patients. Additionally, we used difference and consistency tests to examine the conversion of immunohistochemistry (IHC) markers following NAC. The status of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and molecular subtypes of BC were associated with pCR in the univariate analysis (all P < .05), which may be potential markers to predict pCR. HER2 was identified as an independent factor for predicting pCR in the multivariate analysis. The pCR rate of HER2-positive patients who received NAC combined targeted therapy was higher than that of patients who only received NAC (P = .003). The disease-free survival (DFS) rate of TNBC patients who achieved pCR was significantly higher than that of non-pCR TNBC patients (P = .026). The IHC marker conversion after NAC mainly existed in PR (P = .041). Ki67 expression decreased in the luminal B subtype and increased in the HER2 enriched subtype after NAC (all P < .001). Patients with Ki67 expression change after NAC had longer overall survival (OS) and DFS than unchanged patients (all P < .05). HER2-positive is an independent indicator for predicting pCR, and HE2-positive patients who received NAC combined targeted therapy were favorable to achieving pCR. IHC markers of BC patients exhibit varying degrees of alterations after NAC, and changes in Ki67 expression after NAC could serve as a marker to predict a better prognosis., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To evaluate the role of Ki-67 in predicting subsequent intravesical recurrence following radical nephroureterectomy and to develop a predictive nomogram for upper tract urothelial carcinoma patients., Methods: This retrospective analysis involved 489 upper tract urothelial carcinoma patients who underwent radical nephroureterectomy with bladder cuff excision. The data set was randomly split into a training cohort of 293 patients and a validation cohort of 196 patients. Immunohistochemical analysis was used to assess the immunoreactivity of the biomarker Ki-67 in the tumor tissues. A multivariable Cox regression model was utilized to identify independent intravesical recurrence predictors after radical nephroureterectomy before constructing a nomographic model. Predictive accuracy was quantified using time-dependent receiver operating characteristic curve. Decision curve analysis was performed to evaluate the clinical benefit of models., Results: With a median follow-up of 54 months, intravesical recurrence developed in 28.2% of this sample (n = 137). Tumor location, multifocality, pathological T stage, surgical approach, bladder cancer history and Ki-67 expression levels were independently associated with intravesical recurrence (all P < 0.05). The full model, which intercalated Ki-67 with traditional clinicopathological parameters, outperformed both the basic model and Xylinas' model in terms of discriminative capacity (all P < 0.05). Decision-making analysis suggests that the more comprehensive model can also improve patients' net benefit., Conclusions: This new model, which intercalates the Ki-67 biomarker with traditional clinicopathological factors, appears to be more sensitive than nomograms previously tested across mainland Chinese populations. The findings suggest that Ki-67 could be useful for determining risk-stratified surveillance protocols following radical nephroureterectomy and in generating an individualized strategy based around intravesical recurrence predictions., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

This retrospective study aimed to investigate ethnic disparities in demographic, clinicopathologic, and biological behaviours of gastric cancer (GC) in a high GC incidence area of China. There were 5022 GC patients, including 3987 Han (79.4%) and 987 Hui (14.4%) patients from Northwest China. All patient data were retrieved from 2009 to 2017. Median survival was estimated using the Kaplan-Meier method and compared using the log-rank test. A Cox proportional hazards model was used to assess the impact of covariates. Similarly, low 5-year OS rates were observed in both the Hui and Han groups (23.8% and 24.2% respectively). Hui patients with stage T1 or N0 or with tumours <5 cm had 2.144-fold, 1.426-fold and 1.305-fold increased risks of poor prognosis compared with Han patients with these characteristics respectively (all p < 0.05). Further, Hui patients had 1.265-fold, 1.364-fold and 1.401-fold increased risks of poor prognosis compared with Han patients among those with high expression of Ki67, EGFR and VEGF respectively (all p < 0.05). There are ethnic disparities in the prognosis of GC patients in Northwest China. Understanding the effects of ethnicity on GC will guide reasonable evaluations of prognosis and future interventions to equalise access to high-quality care for GC patients of different ethnicities in China., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background and Objectives: We aimed to explore the capacity of the combined ratio of biomarkers to predict the recurrence of Stage I-III endometrial cancer (EC)., Methods: A total of 473 patients were enrolled after screening. The cut-off value of the ratio was calculated by the receiver operating characteristic curve (ROC). The univariate and multivariate Cox regression analysis was used to assess the correlation between the combined ratio and the recurrence of EC. The differences of clinicopathological parameters between the two groups divided based on the threshold were compared., Result: The ROC curve showed that 0.92 was the optimal cut-off value of the ratio ([ER + PR]/[P53 + Ki67]). The multivariate analysis demonstrated that only International Federation of Gynecology and Obstetrics stage (p = .031) and the combined ratio (p = .004) were independent risk factors of recurrence. The 3-year recurrence-free survival (RFS) and overall survival of patients in the low-ratio group were 54.1% and 66.8%, respectively; while in the high-ratio group were 94.9% and 97.9%, respectively (p < .001). The 3-year RFS of 194 patients, who did not receive the adjuvant therapy, was 54.7% and 97.2% between two groups (p < .001)., Conclusions: The optimal cut-off value (0.92) of the combined ratio was demonstrated to be better to predict the recurrence of EC than a single immunohistochemical marker., (© 2020 Wiley Periodicals LLC.)

Background: This study aimed to comprehensively investigate the effect of spread through air spaces (STAS) on clinicopathologic features, molecular characteristics, immunohistochemical expression, and prognosis in lung adenocarcinomas (ADC) and squamous cell carcinomas (SQCC) based on the 8th edition AJCC/UICC staging system., Methods: In total, 303 ADC and 121 SQCC cases were assessed retrospectively. Immunohistochemical staining was performed for E-cadherin, vimentin, Ki67, survivin, Bcl-2, and Bim. Correlations between STAS and other parameters were analyzed statistically., Results: STAS was observed in 183 (60.4%) ADC and 39 (32.2%) SQCC cases. In ADC, the presence of STAS was associated with wild-type EGFR, ALK and ROS1 rearrangements, low E-cadherin expression, and high vimentin and Ki67 expression. In SQCC, STAS was associated with low E-cadherin expression and high vimentin and survivin expression. Based on univariate analysis, STAS was associated with significantly shorter disease-free survival (DFS) and overall survival (OS) in ADC. In SQCC, STAS tended to be associated with shorter OS. By multivariate analysis, STAS was an independent poor prognostic factor in ADC for DFS but not OS. Stratified analysis showed that STAS was correlated with shorter DFS for stage I, II, IA, IB, and IIA ADC based on univariate analysis and was an independent risk factor for DFS in stage I ADC cases based on multivariate analysis., Conclusions: Our findings revealed that STAS is an independent negative prognostic factor for stage I ADC using the new 8th edition AJCC/UICC staging system. Stage I patients with STAS should be followed up more closely and might need different treatment strategies.

Background: To investigate the clinical and pathological characteristics of appendiceal mucinous adenocarcinoma with peritoneal metastasis and analyze the prognostic factors., Methods: A retrospective analyses of clinicopathological features of 50 patients with appendiceal mucinous adenocarcinoma with peritoneal metastasis from January, 2013 to December, 2017 in Aerospace Central Hospital, Beijing, China. Survival data calculation and comparison were respectively performed with the Kaplan-Meier method and the log-rank test. The Cox proportional hazards regression method was used for multivariate survival analyses., Results: Cytoreduction for appendiceal mucinous adenocarcinoma was conducted on 50 patients (24 males and 26 females), with a median age of 52.5 years at the time of surgery (range 31-71 years). The median overall survival (OS) time was 24 months, with 2-,3- and 5-year survival rates of 53, 24 and 8%, respectively. At the last follow-up in December 2018, 13 patients were still alive. Multivariate analysis revealed that patients who had low Ki-67 expression (less than 50%) and CCR (completeness of cytoreduction) 0/1/2 score had significantly better OS rate than their respective counterparts., Conclusions: Ki-67 expression statue and CCR score could be employed as the prognosis prediction in patients with appendiceal mucinous adenocarcinoma.

Background: An External Quality Assessment (EQA) program was developed to investigate the status of estrogen receptor (ER), progesterone receptor (PR), and Ki-67 immunohistochemical (IHC) detection in breast cancer and to evaluate the reproducibility of staining and interpretation in 44 pathology laboratories in China., Methods: This program was implemented through three specific steps. In study I, three revising centres defined the reference value for 11 sections. In study II, 41 participating centres (PC) stained and interpreted 11 sections by their own daily practice IHC protocols. In study III, all cases received second interpretation opinions., Results: The stained slides of 44 laboratories were up to the interpretation standard. The overall interpretation concordance rate of this study was over 90%. A perfect agreement was reached among the PCs for the cases with ER+ and PR+ > 50% and Ki-67 > 30%, whereas a moderate agreement was observed for intermediate categories. After second interpretations, the misclassification rates for ER were reduced by 12.20%, for PR were reduced by 17.07%, and for Ki-67 were reduced by 4.88%. Up to 31 PCs observed a benefit from the second opinion strategy., Conclusions: This project is the first EQA study performed on a national scale for assessment of ER, PR and Ki-67 status by IHC in China. In the whole IHC evaluation process, the intermediate categories were less reproducible than those with high expression rates. Second opinions can significantly improve the diagnostic agreement of pathologists' interpretations.

Objective: To explore related factors that influence time to recurrence and prognosis of gliomas., Methods: A retrospective analysis of pathologic and clinical data of patients with glioma who underwent surgery for the first time and had a recurrence between 2009 and 2018 in West China Hospital was performed. Clinical characteristics of patients were reviewed, and survival analysis was performed to identify prognostic factors for the recurrent time. Molecules with differential changes in the paired samples were included in the survival analysis., Results: A total of 84 patients met our inclusion requirements and were included in the study; other related factors were also considered in detail in the integrated analysis. Significant differences among O 6 -methylguanine-DNA methyltransferase (positive/negative), isocitrate dehydrogenase 1 (positive/negative), and Ki-67 were determined by statistical analysis of paired samples (P = 0.013, P = 0.014, P = 0.017). Univariate analysis demonstrated that Ki-67 (low expression, medium expression, high expression), initial World Health Organization grade (low or high), tumor side (left, right, middle), age (≥50 years, <50 years), and extent of resection were significantly correlated with time to recurrence (log-rank P = 0.008, P < 0.001, P = 0.015, P < 0.001, P = 0.001). Multivariate analysis results showed that Ki-67 lower expression (hazard ratio [HR] = 0.585, 95% confidence interval [CI] = 0.146-2.336, P = 0.448), medium expression (HR = 0.256, 95% CI = 0.084-0.784, P = 0.017), and high expression (HR = 1 as a reference) together with the initial World Health Organization grade (HR = 0.148, 95% CI = 0.029-0.749, P = 0.021) were independent predictive factors for glioma recurrence., Conclusions: This comprehensive analysis revealed that initial World Health Organization grade and Ki-67 proliferative index were independent prognostic factors that predict the time to recurrence of glioma in patients after first surgery., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: Breast cancer has become the most common cancer in women in China, and the clinicopathological features differ from those in Western patients. This study was performed to investigate the distribution of programmed cell death protein 1 (PD-1) + /PD-1 - tumor-infiltrating lymphocytes (TILs) and its association with clinicopathological features among Chinese patients with breast cancer., Methods: In total, 133 consecutive patients with primary breast cancer were recruited into this cross-sectional study from 2012 to 2013. TILs were measured by cell counts under high-power fields (HPFs). Immunohistochemistry was used to detect PD-1 expression on tumor-infiltrating lymphocytes in the microenvironment., Results: The median cell counts of the overall TILs, PD-1 + TILs, and PD-1 - TILs were 80, 18, and 55/HPF, respectively. The number of PD-1 - TILs was significantly lower in older than younger patients (50 vs. 60/HPF). Patients with positive E-cadherin expression had more PD-1 - TILs than patients with negative E-cadherin expression (57 vs. 27/HPF). The Ki-67 index was positively correlated with the cell counts of PD-1 + TILs, and the correlation coefficient was 0.29., Conclusions: PD-1 expression on TILs had different clinicopathological features in Chinese patients with breast cancer. E-Cadherin expression was associated with PD-1 - TILs; however, Ki-67 expression was associated with PD-1 + TILs.

Mammary analogue secretory carcinoma of salivary gland (MASC) is a tumor with histopathologic and immunophenotypic features mimicking secretory carcinoma of the breast harboring the ETV6 split. The expression of mammaglobin, S-100, Ki-67, P63 and ETV6 split were detected in twelve cases of acinar cell carcinoma and fourteen cases of mammary analogue secretory carcinoma of salivary gland by immunohistochemistry and fluorescence in situ hybridization respectively. The expression of ETV6 gene split was detected in fourteen mammary analogue secretory carcinomas of salivary gland with positive expression of mammaglobin. Eight of mammary analogue secretory carcinomas of salivary gland also tested positive for the ETV6 gene split via fluorescence in-situ hybridization (FISH). The concordance rate of the immunohistochemistry and FISH was 72.3%. Mammaglobin and ETV6 gene split detection could help to distinguish mammary analogue secretory carcinoma of salivary gland. The mammary analogue secretory carcinoma of salivary gland specimens were also examined under transmission electron microscope. And apical junctional complexes were observed in the loosely connected tumor cells., (Copyright © 2017. Published by Elsevier Ltd.)

The objective was to study the relationship among Her-2, Ki-67, p53 expression and the clinicopathologic characteristics of breast cancer in the patients of northern China. Expression of Her-2, Ki-67, p53 and clinical characteristics of 260 breast cancer patients were retrospectively studied. Her-2 overexpression led to higher incidence rates of infiltrating ductal carcinoma and axillary lymph node metastasis, bigger diameters of the primary tumors, later pTNM staging, and a lower incidence rate of ductal carcinoma in situ (p < 0.05). High expression of ER and PR led to fewer patients classified histologically in higher grade (p = 0.001), while high expression of Ki-67 and p53 caused more patients classified histologically in higher grade (p = 0.001). In patients histologically classified in grade 1 and 2, the expression of Ki-67 and p53 was significantly (p = 0.001) higher, and the expression of ER and PR was significantly lower, in Her-2 positive patients than Her-2 negative patients. Breast cancer with Her-2 overexpression was more likely to recur and metastasize than Her-2 negative breast cancer. Higher coincidence of high expression of p53 and Ki-67 with Her-2 overexpression and more progressed tumors suggested that in addition to p53, Ki-67 might also be a prognostic biomarker of breast cancer.

In this study, we examined the expression and prognostic value of fibrous sheath interacting protein 1 (FSIP1) in 202 non-small cell lung cancer (NSCLC) patients who underwent lung cancer resection at Shengjing Hospital of China Medical University. FSIP1 mRNA and protein expression were measured in NSCLC tissues and non-tumor adjacent tissues (NATs), and Harrell's concordance index (c-index) was used to evaluate the ability of FSIP1 to predict prognosis. FSIP1 mRNA and protein expression was higher in NSCLC tissues than in NATs. Survival analysis revealed the 5-year overall survival rate to be 35.4% in the FSIP1-positive group and 56.3% in the FSIP1-negative group, and FSIP1-positive status was an independent prognostic factor for poor overall survival. The c-index value of FSIP1 for overall survival was greater than that of Ki67, and the addition of FSIP1 status increased the c-index value of the TNM staging system. These results suggest that evaluating FSIP1 status in addition to TNM stage during routine pathological examinations could improve prognostic predictions in NSCLC patients.

Background/aims: Hepatocellular carcinoma (HCC) is a common malignant tumor with a high rate of recurrence. Immunohistochemical analysis of the marker of proliferation Ki-67 (MKI67) is used to assess proliferation activity of HCC The regulation of MKI67 expression remains unclear in HCC This study aims to explore the association between MKI67 expression and gene variants., Methods: A total of 195 hepatitis B virus (HBV)-related HCC patients were genotyped using Illumina HumanExome BeadChip-12-1&#95;A (242,901 markers). An independent cohort (97 subjects) validated the association of polymorphism determinants and candidate genes with MKI67 expression. The relationships between MKI67 with p53 and variants of candidate genes in the clinical outcomes of HCC patients were analyzed., Results: We found that MKI67 combined with p53 was associated with a 3-year recurrence-free survival and five variants near TTN and CCDC8 were associated with MKI67 expression. TTN harboring rs2288563-TT and rs2562832-AA+CA indicated a favorable outcome for HCC patients., Conclusion: Variants near TTN and CCDC8 were associated with MKI67 expression, and rs2288563 and rs2562832 in TTN are potential biomarkers for the prediction of clinical outcomes in HBV-related HCC patients., (© 2017 The Author(s). Published by S. Karger AG, Basel.)

Purpose: The heterogeneous nature of the mucinous breast cancer (MBC), with its pure (PMBC) and mixed subtypes (MMBC), calls for precise prognosis assessment., Methods: We analyzed 197 consecutive MBC patients, including 117 PMBC and 80 MMBC, who were treated from 1983 to 2014. The clinicopathological features, treatment choice, disease-free survival (DFS) and overall survival (OS) were compared among PMBC, MMBC and MMBC subgroups. Prognostic factors of PMBC and MMBC were identified., Results: Compared to PMBC, MMBC had more lymph node metastasis (p = 0.043), Her2 positivity (p = 0.036), high Ki-67 index (defined as>20%, p = 0.026) and anti-Her2 targeted therapy (p = 0.016). The 5-year DFS of PMBC and MMBC were 90.4% and 86.2%, whereas the 5-year OS were 99.0% and 98.7%. No significant difference was found in DFS or OS among all MBC subtypes. High Ki-67 (p = 0.020) appeared as DFS factor in PMBC, while anti-Her2 targeted therapy (p = 0.047) as the DFS predictors in MMBC., Conclusion: MMBC manifested similar 5-year survival to PMBC in Chinese woman, suggesting that intra-tumoral heterogeneity might not interfere with MBC short-term prognosis., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To analyze the clinical performance of p16/Ki-67 dual-stained cytology identifying high-grade cervical intraepithelial neoplasia (CIN2+) in Chinese women., Methods: 1079 women attending ongoing cervical cancer screening and 211 "enriched" women aged ≥30yrs with biopsy-confirmed CIN2+ from five Chinese hospitals were enrolled during year 2014-2015. Cervical specimens were collected for high-risk human papillomavirus (HR-HPV) DNA analysis, Liquid-based cytology (LBC) and p16/Ki-67 dual staining. Colposcopy and biopsy were performed on women with any abnormal result., Results: p16/Ki-67 positivity increased with histologic severity. It was 18.4%(183/996) in normal histology, 54.0%(34/63) in CIN1, 81.0%(34/42) in CIN2, 93.3%(111/119) in CIN3, 71.4% (5/7) in adenocarcinoma and 95.2%(60/63) in squamous cell carcinoma. Compared with the HR-HPV negatives, p16/Ki-67 expression was significantly higher in the HPV16/18 positive (OR: 35.45(95%CI: 23.35-53.84)) and other 12 HR-HPV types positive group (OR: 8.01(95%CI: 5.81-11.05). The sensitivity and specificity of p16/Ki-67 to detect CIN2+ in the entire population were 90.9% and 79.5%, respectively. In women with ASC-US and LSIL, sensitivity and specificity for detection of CIN2+ were 87.5% and 66.4%, respectively, with a referral rate of 43.8%. In women who tested positive for HR-HPV, sensitivity and specificity of dual-staining for detection of CIN2+ were 92.7% and 52.7%, respectively, and the referral rate was 68.7%., Conclusions: p16/Ki-67 dual-stained cytology provided a high sensitivity and moderate specificity to detect underlying cervical precancer and cancers in various settings, and might be considered as an efficient screening tool in China., Competing Interests: All the authors declare that they have no competing interests.

Objective: To study the clinicopathologic characteristics of primary salivary gland-type lung carcinomas, and the immunophenotypic value of TTF-1, Napsin A and Ki-67 in their differential diagnosis., Methods: Totally 48 special type lung cancer surgical removal specimens were collected in China-Japan Friendship Hospital during September 2009 to December 2014. A panel of immunohistochemical markers (TTF-1, Napsin A, Ki-67, CK5/6, CK7 and p63) were conducted on these specimens., Results: The 48 cases of special type lung cancer included 25 cases of primary salivary gland-type lung carcinoma (18 cases of adenoid cystic carcinoma and 7 cases of mucoepidermoid carcinoma), 5 cases pulmonary adenocarcinoma with mucoepidermoid carcinoma-like or adenoid cystic carcinoma-like structure, and 18 cases of pulmonary adenosquamous carcinoma. Compared with pulmonary adenocarcinoma with mucoepidermoid carcinoma-like or adenoid cystic carcinoma-like structure and pulmonary adenosquamous carcinoma, primary salivary gland-type lung carcinomas have special characteristics in median age, sex, location, tumor size, LN involvement and pleura invasion, with negative TTF-1 and Napsin A expression as well as lower Ki-67 index detected by immunohistochemistry. Primary salivary gland-type lung carcinomas usually have an indolent behavior., Conclusions: Primary salivary gland-type lung carcinomas are low-aggressive entities. The origins of primary salivary gland-type lung carcinomas were different from that of pulmonary adenocarcinoma with mucoepidermoid carcinoma-like or adenoid cystic carcinoma-like structure and pulmonary adenosquamous carcinoma. Negative TTF-1 and Napsin A expression as well as Ki-67 index lower than 20% have special value for primary salivary gland-type lung carcinomas in their differential diagnosis.

Accumulating evidence demonstrates that defining molecular subtypes based on objective genetic alterations may permit a more rational, patient-specific approach to molecular targeted therapy across various cancers. The objective of this study was to subtype primary glioblastoma (pGBM) based on MicroRNA (miRNA) profiling in Chinese population. Here, miRNA expression profiles from 82 pGBM samples were analyzed and 78 independent pGBM samples were used for qRT-PCR validation. We found that two distinct subgroups with different prognosis and chemosensitivities to temozolomide (TMZ) in Chinese pGBM samples. One subtype is TMZ chemoresistant (termed the TCR subtype) and confers a poor prognosis. The other subtype is TMZ-chemosensitive (termed the TCS subtype) and confers a relatively better prognosis compared with the TCR subtype. A classifier consisting of seven miRNAs was then identified (miR-1280, miR-1238, miR-938 and miR-423-5p (overexpressed in the TCR subtype); and let-7i, miR-151-3p and miR-93 (downregulated in the TCR subtype)), which could be used to assign pGBM samples to the corresponding subtype. The classifier was validated using both internal and external samples. Meanwhile, the genetic alterations of the TCR and TCS subtypes were also analyzed. The TCR subtype was characterized by no IDH1 mutation, and EGFR and Ki-67 overexpression. The TCS subtype displayed the opposite situation. Taken together, the results indicate a distinct subgroup with poor prognosis and TMZ-chemoresistance.

The classification of luminal breast cancer has been a popular topic regarding its heterogeneity with distinct biological features and clinical outcomes. This study aimed to assess the power of proliferative indices (Ki67 and histological grade) to determine various clinicopathological characteristics and survival in luminal disease. A total of 541 patients with stage I-III luminal breast cancer were enrolled. Subtypes were determined using proliferative indices and were compared with clinicopathological variables and short-term survival. The significance of various treatments was evaluated in a subgroup of pN0 (lymph node negative) patients. Histological grade, independent of other variables, was a better predictor in the ER/PR+, human epidermal growth factor receptor 2 (Her-2) subgroup (p = 0.011) and the pN0 subgroup (p = 0.044) compared with Ki67, which only showed significance in the ER/PR+, Her-2 subgroup (p = 0.008). Neither grade nor Ki67 was associated with outcomes in the luminal Her-2 class. In pN0 patients, various treatments did not show significance in short-term survival. Histological grade outperformed Ki67 as a determinant for the stratification of luminal class regarding short-term survival. Chemotherapy most likely did not provide additional benefit to pN0 patients with luminal breast cancer compared with endocrine therapy.

The aim of this study was to study the prevalence and clinicopathologic features of breast cancer patients with type 2 diabetes mellitus in southwest of China for providing clinical guidance and prognosis appreciation for these patients. Through a case-control study of 3,381 primary breast cancer patients initially diagnosed from January 2007 to May 2013, one case group (164 female breast cancer patients with type 2 diabetes) and two control groups (first control group consists of 328 randomly selected nondiabetic breast cancer patients and second control group consists of 279 nondiabetic breast cancer patients without diabetes-related diseases such as cardiovascular or cerebrovascular diseases) were selected. The clinicopathological features between them were statistically analyzed. (1) Of 3,381 primary breast cancer patients with the average age of 50.5, ranging from 21 to 97 years of age, 164 (4.9 %) cases (with the average age of 60.7) suffered diabetes (previously diagnosed diabetes). (2) The differences of clinicopathologic features between the case group and first control group (with the average age of 61.5) were the ratio of hypertension (41.5 vs 26.1 %, P = 0.001) and axillary lymph node metastasis (51.1 vs 38.1 %, P = 0.046); and the differences of clinicopathologic features between the case group and second control group (with the average age of 64.3) were axillary lymph node metastasis (51.1 vs 35.8 %, P = 0.017), tumor size (≥ T2: 62.3 vs 53.1 %, P = 0.019) and p53 expression (51.0 vs 62.7 %, P = 0.018). No statistical significances (P > 0.05) of histological type, histological grade, or the expressions of estrogen receptor (ER), progesterone receptor, human epidermal growth factor 2 (HER2) and Ki67 were found between them. (3) The clinicopathologic features of ER-positive and ER-negative patients in each group were as follows: (1) In the case group, the ER-negative patients have more advanced tumor histological grade (G3, 19.0 vs 2.8 %, P = 0.012), more positive expression of Her-2 (16.9 vs 8.1 %, P = 0.029) and more axillary lymph node metastasis (63.3 vs 44.4 %, P = 0.048). (2) In the first control group, the same results with tumor histological grade (G3, 15.6 vs 6.2 %, P = 0.025) and positive expression of Her-2 (16.7 vs 4.3 %, P = 0.001), and more positive expression of Ki67 (65.1 vs 52.0 %, P < 0.001) were found. (3) In the second control group, the ER-negative patients have more positive expression of Ki67 (70.5 vs 55.7 %, P = 0.009) and fewer family history of malignancy (1.9 vs 10.0 %, P = 0.013). Diabetes has a high incidence in breast cancer patients and is more common with postmenopausal patients. It is suggested that initially diagnosed breast cancer patients should undertake oral glucose tolerance test screening for occult diabetes and prediabetes. More concerns should be put onto diabetic patients with breast cancer.

We aimed to investigate risk factors of local and distant recurrence in small-sized, node negative breast cancer in women <35 years in a Chinese cohort. Between January 1994 and January 2007, 107 patients with pathologically confirmed small-sized ([Symbol: see text]1 cm), node negative breast cancer who did not receive neoadjuvant or adjuvant chemotherapy were included. The 5-year recurrence-free survival (RFS) was estimated according to different prognostic variables. With a median time of 60 months (range, 8-60 months) follow-up, local and distant recurrence were observed in 25 cases (23.4%). By univariate analysis, HER-2 positivity, triple negative (TN), and high Ki-67 index ([Symbol: see text]14%) were risk factors of a lower RFS (hazard ratio (HR) 6.680, 95% confidence interval (CI) 2.350-18.985, P<0.0001 for HER-2 positive; HR 4.769, 95%CI 1.559-14.591, P=0.006 for TN; HR 6.030, 95%CI 2.659-13.674, P<0.0001 for high Ki-67 index). Patients with grade 3 tumors had a lower RFS (HR 2.922, 95%CI 1.096-7.791, P=0.032) compared with those with grade 1 or grade 2 tumors. By multivariate analysis, HER-2 positivity (HR 10.204, 95%CI 3.391-30.704, P<0.0001), TN (HR 10.521, 95% CI 3.152-35.113, P<0.0001) and high Ki-67 index (HR 10.820, 95%CI 4.338-27.002, P<0.0001) remained risk factors of RFS. In this cohort, HER-2 positivity, triple negative and high Ki-67 index were independent risk factors of RFS in young patients with T1a,bN0 breast cancer. Subsequent pregnancy did not affect RFS.

Gastric intestinal metaplasia can display cytoarchitectural atypia that falls short of qualifying for dysplasia but can be classified as indefinite for dysplasia. Yet few studies have evaluated the prevalence, the morphologic, and biologic characteristics of this variant. Out of a cohort of 554 biopsies with chronic atrophic gastritis and/or dysplasia, we categorized the cases as either (1) simple intestinal metaplasia; (2) intestinal metaplasia with hyperplasia; (3) intestinal metaplasia with basal gland atypia; and (4) gastric dysplasia. The relationship between the subtypes and various clinicopathologic features, mucin immunophenotypes, and biologic characteristics was evaluated. The final cohort consisted of 424 cases of simple intestinal metaplasia, 93 intestinal metaplasia with hyperplasia, 16 intestinal metaplasia with basal gland atypia, and 21 gastric dysplasia. Intestinal metaplasia with basal gland atypia had a prevalence of 2.8% and similar to gastric dysplasia, 3.7%. Both of these lesions were similar in body/fundus distribution (12.5%) and paucity of goblet cells (68.8%). Intestinal metaplasia with basal gland atypia and gastric dysplasia seem to share some biologic similarities but with a lower frequency of alpha-methylacyl-CoA racemase expression (25% versus 62%), p53 expression (6.3% versus 47.6%), and increased Ki-67 index on surface/pit and isthmus in intestinal metaplasia with basal gland atypia. Alternatively, simple intestinal metaplasia and intestinal metaplasia with hyperplasia did not differ statistically with regard to the various characteristics evaluated. We concluded that gastric intestinal metaplasia can be divided into 2 broad categories that are readily defined by cytoarchitectural and biologic characteristics. Based on the characteristics of intestinal metaplasia with basal gland atypia and in keeping with others, we confirm that this subtype could represent a preneoplastic lesion that needs further evaluation., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Patients with diffuse large B-cell lymphoma (DLBCL) can be divided into germinal center B-cell-like subtype (GCB-DLBCL) and activated B-cell-like type (ie non-GCB-DLBCL) and with a prognostic value based on the cell of origin of the tumor as determined by microarray analysis, as well as by immunostain algorithms. To stratify primary breast DLBCL, according to immunostain algorithms of Hans, Choi, and Meyer (Tally), the reason why primary breast DLBCL possesses a poor clinical outcome was further elucidated. Twenty-two cases of primary breast DLBCL, diagnosed according to the 2008 World Health Organization classification of tumors of hematopoietic and lymphoid tissues, were retrospectively studied. Immunochemical study was performed, and follow-up information was analyzed. The histopathologic and immunophenotypic features of all cases were summarized. Among these 22 cases, most (17, 16, and 17, respectively) were assigned to the activated B-cell-like subtypes, few (5, 6, and 5, respectively) were classified as GCB-DLBCL subtype. Fourteen of these 22 cases expressed high proliferative activity (≥40% Ki-67 labeling). Most primary breast DLBCLs have activated B-cell-like subtype characteristics and high proliferative activity; these features might be a significant factor., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The purpose of this study is to investigate the mixed lineage leukemia gene (MLL, located on chromosome 11q23) expression in T acute lymphoblastic leukemia (T-ALL)/lymphoblastic lymphoma (LBL) and its relationship to prognosis. Fifty cases of T-ALL/LBL with clinical data were selected from the Shanxi Cancer Hospital in China. The immunohistochemical EnVision method was used for the expression of CD3, CD7, CD10, CD20, CD23, CD43, CD45RO, CD99, terminal deoxynucleotidyl transferase, myeloperoxidase and ki67. Fluorescent in situ hybridization for MLL gene expression was performed on paraffin-embedded tissue. Among the 50 cases of T-ALL/LBL, the percentages of tumor cells expressing terminal deoxynucleotidyl transferase, CD99, CD3, CD7, CD10, CD43, and CD45RO were 92.0%, 96.0%, 72.0%, 92.0%, 34%, 60.0%, and 40.0%, respectively, whereas myeloperoxidase, CD20, and CD23 were all negative. A level of Ki67 expression >80% was found in 18 cases and ≤80% in 32 cases. The period of follow-up ranged from 1 to 108 months. The overall survival rate was 35.8%, with a median survival time of 330 days. Breakage of 11q23 was detected in 8 (16.00%) and amplification in 14 (28.00%) of the 50 cases. The rate of amplification in stage III-IV was higher than that in stage I-II (P<0.05). The prognosis in the 11q23 breakage group was worse than that in the nonbreakage group (P<0.05). The prognosis in the 11q23 amplification group was also worse than that in the nonamplification group (P<0.05). MLL gene rearrangement is a new subgroup concerned with prognosis in T-ALL/LBL. Both breakage and amplification of 11q23 in T-ALL/LBL might play important roles in the development and progression of T-ALL/LBL.

Background: To evaluate the expression and differential diagnostic significance of CK19, TG, Ki67 and galectin-3 in papillary thyroid carcinoma (PTC) (metastatic and non metastatic), follicular adenoma and nodular goiter in patients from the northeastern part of China., Methods: 441 PTC specimens and 151 other benign thyroid specimens (97 cases of nodular goiter, 54 cases of nonmalignant follicular adenoma) were collected. Immunohistochemistry for CK19, TG, Ki67 and galectin-3 was performed., Results: CK19, TG, Ki67 and galectin-3 expression was 96.37% (425/441), 82.77% (365/441), and 40.59% (179/441), 96.82% (427/441), respectively, for the PTC group and the expression of these markers in the benign thyroid lesions group was 25.83% (39/151), 79.47% (120/151), and 37.09% (56/151), 50.99% (77/151), respectively. The expression of CK19 and galectin-3 in PTC was much higher than that in the nonmalignant group (p < 0.05). However, the expression of TG, Ki67 did not differ among these two groups (p > 0.05). The diagnostic efficiency of CK19 and galectin-3 for PTC was 96.37% (537/592) and 84.63% (501/592). CK19 and galectin-3 expression rate in PTC was higher than that in benign disease cases., Conclusions: The diagnostic efficiency of CK19 for PTC was slightly better than galectin-3. The utilization of these markers combined with morphologic evaluation may be helpful in the differential diagnosis of papillary thyroid carcinoma in the northeastern region of China.

SIRT1 is a deacetylase that modifies gene expression. Some researchers have found that SIRT1 is upregulated in malignant tumor tissues. Therefore, this study investigated the SIRT1 expression in gastric cardiac carcinoma and its correlation with clinicopathologic features and prognosis. Tissue microarray technique and immunohistochemical stains were used to detect the expression of SIRT1, p53, and Ki-67 in 176 gastric cardiac carcinoma tissues and 32 normal gastric cardiac region tissues. SIRT1 expression in gastric cardiac carcinoma was significantly higher than that in normal gastric cardiac tissues and was associated with lymphatic metastasis, TNM stage, survival rate and mean survival time. Expression of Ki-67 in the SIRT1 positive group was significantly higher than that in the negative group. In conclusion, high expression of SIRT1 in gastric cardiac carcinoma was correlated with lymphatic metastasis, TNM stage, proliferative status and prognosis. SIRT1 might be a biological parameter to evaluate malignant degree and prognosis of gastric cardiac carcinoma.

Background: The aim was to describe the clinicopathological features and prognosis of young patients with breast cancer., Patients and Methods: We reviewed the records of 1478 consecutive patients aged ≤50 years with first diagnosis of invasive breast cancer referred to surgery from January 1999 to March 2005. A total of 174 patients were aged <35 years (group I) and 1304 were aged 35-50 years (group II)., Results: Compared with patients of group II, patients of group I had a higher percentage of tumors classified as estrogen receptors (ER) negative, progesterone receptors (PR) negative, with a Ki-67 labeling index ≥20% of the cells. The 5-year survival of group I was 78.3% as compared with 84.2% for group II (P = 0.006)., Conclusion: Compared with patients aged between 35 and 50 years, patients aged <35 years have a greater chance of having an endocrine-unresponsive tumor and a significantly poor prognosis., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Recent genome-wide association studies have identified seven single nucleotide polymorphisms (SNPs) associated with breast cancer, but mainly in Europeans. In this study, the authors evaluated the effect of these loci on breast cancer and its disease characteristics in women from northeast of China, Heilongjiang Province. Seven SNPs were successfully genotyped in 492 breast cancer patients and 510 healthy controls using the SNaPshot method. The associations between SNPs and breast cancer were examined by logistic regression. The associations between SNPs and disease characteristics were examined by the chi-square test or one-way ANOVA as needed. The authors confirmed the effects of the allele A for rs2046210 at 6q25 on increased breast cancer risk in the population, with odds ratio 1.417 (P = 2×10⁻⁴). However, no significant association was detected between SNPs from TNCR9, LSP1, MAP3K1, 2q35, and 8q24 and breast cancer. Analyses of the disease characteristics showed that SNP rs2046210 was associated with age at menopause (P = 0.001). MAP3K1 SNP rs889312 and LSP1 SNP rs3817198 were associated with HER2 status in the patient cohort (P = 0.036 and P = 0.005, respectively). And SNP rs3817198 was also associated with the combined status of estrogen receptor, progesterone receptor, and HER2 (P = 0.012). SNP rs13281615 was associated with age at menarche (P = 0.023), and SNP rs3803662 was associated with average duration of breastfeeding (P = 0.036). All other disease characteristics, including tumor grade, clinical stage, and the status of estrogen receptor or P53, were not significantly associated with any of these variants. These results suggested that the rs2046210 was associated with breast cancer in a Northern Chinese population, and some SNPs were also associated with breast cancer characteristics.

Minichromosome maintenance proteins are novel proliferative markers that have been proposed as diagnostic markers in many cancers. We evaluated the potential role of minichromosome maintenance protein 2 as a screening biomarker and compared it with proliferating cell nuclear antigen and Ki67 in a population survey of esophageal squamous cell carcinoma. A total of 299 esophageal samples from a high-risk region in China, including 171 from an endoscopy population survey, 30 from brushing cytology, and 98 from surgery and autopsy, underwent immunostaining with minichromosome maintenance protein 2, proliferating cell nuclear antigen, and Ki67 antibodies. Minichromosome maintenance protein 2 expression was confined to the proliferative compartment of normal and abnormal esophageal epithelium and particularly manifested in the surface layer of dysplasia and carcinoma in situ. The expression of proliferating cell nuclear antigen and Ki67 was positively correlated with that of minichromosome maintenance protein 2 (r(s) >0.39, P < .01); but their positive nuclei seldom reached the surface layer, and the labeling indices were significantly lower than those for minichromosome maintenance protein 2 in dysplasia (P < .05) and carcinoma in situ (P < .001). The sensitivity and specificity of minichromosome maintenance protein 2 in diagnosing dysplasia were 91.3% and 61.8%, respectively, higher than those for proliferating cell nuclear antigen (88.4% and 47.1%) and Ki67 (78.3% and 57.8%). Nine of 10 cancer and paracancerous surface-brushing samples expressed minichromosome maintenance protein 2, and the detection was higher than that for proliferating cell nuclear antigen (8/10 and 7/10) and Ki67 (7/10 and 7/10). However, none of 10 normal surface-brushing samples expressed the 3 markers. Minichromosome maintenance protein 2 is more sensitive and specific than proliferating cell nuclear antigen and Ki67 in indicating esophageal dysplasia. Minichromosome maintenance protein 2 immunostaining combined with surface brushing could be valuable in screening patients at high risk of cancer in mass surveys., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Cysteine-rich protein 61 (Cyr61) selectively binds heparin and insulin-like growth factors and mediates a variety of biological actions, including cell adhesion, differentiation, proliferation, migration, angiogenesis, and tumorigenesis. Cyr61 is also a prognostic factor for tumor progression and survival of individuals with various types of tumors. This study investigated the relationship between the expression level of Cyr61 and clinicopathological features, as well as the prognostic significance of Cyr61 expression in human salivary adenoid cystic carcinoma (SACC). The expression of Cyr61 and Ki-67, a cell-proliferation marker, was examined immunohistochemically in paraffin embedded tissue specimens from 60 SACC patients who underwent radical surgery between 1995 and 2004. A chi-square test was used to investigate the relationship between Cyr61 and Ki-67 expression and clinicopathological features. Survival analysis was performed to determine the prognostic significance of Cyr61 expression. Cyr61 expression was observed in 39 cases (39/60, 65%) of SACC, and Cyr61 expression was positively correlated with Ki-67 expression (P=0.002). A high expression of Cyr61 was significantly associated with solid subtype, perineural invasion, vascular invasion or cancer embolus, advanced stage, recurrence, and metastasis (P<0.05). The survival rate of patients with high expression of Cyr61 or Ki67 was significantly lower than that of patients with low expression. Multivariate Cox's proportional hazards analysis showed that vascular invasion, TNM stage, recurrence, distant metastasis, Ki-67 expression, and Cyr61 expression were independent prognostic factors of overall survival (P<0.05). Cyr61 expression is significantly correlated with Ki-67 expression and may have potential value in screening high-risk cases for recurrence and metastasis, as well as identifying poor prognosis in SACC patients., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objective: To study the expression and significance of fragile histidine triad (FHIT) and Ki-67 in transformed epithelial cells induced by Yunnan tin mine dust., Methods: Every second generation of immortalized human bronchial epithelial cells (BEAS-2B) and human embryo lung fibroblasts (WI-38) were exposed to 100 µg/ml Yunnan tin mine dust for 72 h, until the ninth generation. The cells were subsequently co-cultured from the 11th generation. Experimental setup: B group, B (W) group, B (W 100) group, B100 group, B100 (W) group, B100 (W100) group. The expressions of FHIT and Ki-67 in epithelial cells were determined by the method of immunocytochemistry at the 16th, 26th and 36th generation. The percentage of Ki-67 positive cells was calculated as proliferation index., Results: The expression of FHIT was observed in BEAS-2B cells. The expression levels of FHIT among B group, B (W) group and B (W 100) group had not instinctive difference. At the 16th generation, the expression of FHIT in the B100 group was decreased compared with that in the B group and the expression of FHIT between B100 (W) group and B100 (W100) group was lower than that in the B100 group. At the 26th generation, the expression of FHIT was decreased compared with that at the 16th generation in the B100, B100 (W) and B100 (W100) groups. However, At the 36th generation, positive expression were observed again in the B100, B100 (W) and B100 (W100) groups and the expression levels were in incremental order. At the 16th, 26th and 36th generation, the proliferation indexes of B group, B (W) group and B (W 100) group were all < 3%. The proliferation indexes of B100, B100 (W) and B100 (W100) were increased step by step with the generation elongation., Conclusions: FHIT could be a target at which Yunnan tin mine dust induces transformation of BEAS-2B cells. The proliferation activation of BEAS-2B cells can be improved by Yunnan tin mine dust.

Calcifying odontogenic cysts (COCs) represent a group of rare odontogenic lesions with a diversity of clinicopathological and behavioral features. According to the WHO classification of head and neck tumors in 2005, COC has been divided into calcifying cystic odontogenic tumor (CCOT), dentinogenic ghost cell tumor (DGCT) and ghost cell odontogenic carcinoma (GCOC). With few reports available on its immunohistochemical profile, this study investigated the histopathological features and the expression of nuclear factor kappaB (NF-kappaB), Ki-67 and matrix metalloproteinase-9 (MMP-9) in CCOT, DGCT and GCOC. According to the WHO classification of head and neck tumors in 2005, 26 cases of the so-called COC were diagnosed as CCOT (n=14), DGCT (n=7) and GCOC (n=5), respectively. The specimens of 26 COCs and 10 classic ameloblastomas (as control group) were examined by immunohistochemistry using anti-NF-kappaB p65, anti-Ki-67 and anti-MMP-9 antibodies and by in situ hybridization(ISH)using anti-MMP-9 mRNA probes. Immunohistochemical reactivity for NF-kappaB was mainly detected in the cytoplasm of tumor cells, and nuclear reactivity was only seen in few tumor cells in COC and classic ameloblastomas. Rate of nuclear staining was less than 1%. The expression of Ki-67 in GCOC was significantly higher than those in CCOT (p<0.001), DGCT and ameloblastoma (p<0.005). In COCs and ameloblastomas, expression of MMP-9 mRNA and protein was detected in tumor cells as well as in stromal cells. The positive staining for MMP-9 protein was detected in stromal cells of all GCOC cases and was significantly stronger than those in CCOT and DGCT groups (p<0.05). NF-kappaB may minimally affect the progression and local invasiveness of CCOT, DGCT and GCOC. GCOC show significantly higher proliferative activity than CCOT and DGCT. MMP-9 in stroma is associated with invasive ability of the CCOT, DGCT and GCOC.

Background: For the female population in Asia, systematic investigation on alterations of cyclin D1 in breast carcinoma is rare, and correlation between cyclin D1 expression with clinicopathological parameters, survival rate, and other prognostic marker associated with cell cycle is unclear., Methods: Expression of cyclin D1 protein, Ki-67, pRb, and p53 was determined by immunohistochemistry in 18 cases of early breast carcinomas and 80 cases of invasive ductal carcinomas. Genetic alteration of cyclin D1 gene and overexpression of cyclin D1 mRNA were detected by Southern blot and RT-PCR, respectively., Results: Expression of cyclin D1 is negative in usual ductal hyperplasia (UDH) and atypical ductal hyperplasia (ADH). However, in 52.0% (51/98) of all breast carcinomas, positive expression of cyclin D1 was observed. Five-year survival rate of the patients with positive expression of cyclin D1 (52.7%) is significantly lower than the cases with negative expression of cyclin D1 (72.1%). Positive rate of cyclin D1 protein in invasive ductal carcinoma (52.5%) is slightly higher than overexpression rate (40.8%) of cyclin D1 mRNA but significantly higher than amplification rate of cyclin D1 gene (18.4%). Expression of cyclin D1 is correlated with Ki-67 expression, but not correlated with pRb and p53 expression., Conclusions: Positive expression of cyclin D1 could serve as a poor prognostic marker for Chinese patients with breast carcinoma independent of nodal metastasis and clinical stage. Expression of cyclin D1 protein is affected more directly by overexpression of cyclin D1 mRNA rather than cyclin D1 gene amplification. The cooperation between pRb and p53 with cyclin D1 protein in the carcinogenesis of breast carcinoma is not supported by the results.

Objective: To describe the fine needle aspiration cytology findings of apocrine carcinoma of breast and correlate them with the histologic appearance., Study Design: The author reviewed the fine needle aspiration cytology findings of two cases of pure apocrine carcinoma of the breast in the files of Pamela Youde Nethersole Eastern Hospital during a three-year period, 1998-2000., Results: The cytologic findings in both cases were similar. The smears were of moderate to high cellularity, consisting of predominantly dispersed or loosely cohesive tumor cells in a focally granular background. The carcinoma cells contained abundant, dense to granular cytoplasm; round or oval and sometimes eccentrically located nuclei; a smooth nuclear outline; evenly dispersed chromatin; and solitary macronucleoli. The cell borders were mostly discrete. In contrast to benign apocrine cells, the malignant cells showed nuclear overlapping, more frequent nuclear pleomorphism, increased nuclear/cytoplasmic ratios and occasional mitotic figures. Histologic examination of the excised specimens showed extensive, solid apocrine carcinoma in situ with focal stromal invasion., Conclusion: Apocrine carcinoma, a subtype of breast carcinoma characterized mainly by its cytologic features, needs to be distinguished from benign apocrine lesions or other eosinophilic and granular cell tumors of the breast. Recognition of the subtle cytologic differences renders a definitive preoperative diagnosis possible.