External quality assessment survey for SARS-CoV-2 nucleic acid amplification tests in clinical laboratories in Tokyo, 2021.

INTRODUCTION: Nucleic acid amplification tests (NAATs) play a pivotal role in clinical laboratories for diagnosing COVID-19. This study aimed to elucidate the accuracy of these tests. METHODS: In 2021, an external quality assessment of NAATs for SARS-CoV-2 was conducted in 47 laboratories in Tokyo, Japan. In open testing, where the laboratories knew that the samples were intended for the survey, a simulated nasopharyngeal swab suspension sample was used, featuring a positive sample A with a viral concentration of 50 copies/µL, positive sample B with 5 copies/µL, and a negative sample. Laboratories employing real-time RT-PCR were required to report cycle threshold (Ct) values. In blind testing, where the samples were processed as normal test samples, a positive sample C with 50 copies/µL was prepared using a simulated saliva sample. RESULTS: Of the 47 laboratories, 41 were engaged in open testing. For sample A, all 41 laboratories yielded positive results, whereas for sample B, 36 laboratories reported positive results, 3 laboratories reported "test decision pending", 1 laboratory reported "suspected positive", and 1 laboratory did not respond. All 41 laboratories correctly identified the negative samples as negative. The mean Ct values were 32.2 for sample A and 35.2 for sample B. In the blind test, six laboratories received samples. Sample C was identified as positive by five laboratories and negative by one laboratory. CONCLUSIONS: The nature of the specimen, specifically the saliva, may have influenced the blind test outcomes. The identified issues must be meticulously investigated and rectified to ensure accurate results.

Multisource surveillance conducted by the Tokyo Metropolitan Government during the Tokyo 2020 Olympic and Paralympic Games.

The Tokyo 2020 Olympic and Paralympic Games (the Games) were held from 23 July to 5 September 2021 in Tokyo, Japan, after a 1-year delay due to the coronavirus disease (COVID-19) pandemic. The Tokyo Metropolitan Government was responsible for monitoring and responding to infectious disease outbreaks other than COVID-19 during the Games. A multisource surveillance system was used from 1 July to 12 September 2021 for the early detection and rapid response to infectious diseases. This included routine notifiable disease surveillance, sentinel surveillance, syndromic surveillance, cluster surveillance, ambulance transfer surveillance and the Tokyo Infectious Alert system. Daily reports were disseminated summarizing the data collected from the multisource surveillance system. No case of infectious disease under the Tokyo Metropolitan Government system required a response during the Games. The multisource surveillance was useful for providing intelligence during the Games and, if required, could contribute to the early detection and rapid response to outbreaks during other mass gatherings. The system could be improved to overcome the challenges implied by the findings of this multisource surveillance.

Genetic Characteristics of the Virus Detected in the First Mpox Imported Case in Tokyo, Japan.

Mpox, caused by the mpox virus (MPXV), produces symptoms similar to those of smallpox when transmitted to humans. Since 1970, this disease has been endemic, particularly in Africa. However, since May 2022, the number of patients without a history of travel to endemic areas has increased rapidly globally. Under these circumstances, in July 2022, two different real-time PCR methods were used on specimens brought to the Tokyo Metropolitan Institute of Public Health. MPXV was detected in the skin samples, and it was inferred that the virus was a West African strain. Furthermore, a more detailed analysis of the genetic characteristics of the detected MPXV using next-generation sequencing revealed that the MPXV detected in Tokyo was strain B.1, which corresponds to the same strain that is prevalent in Europe and the USA. This suggests that mpox reported for the first time in Japan was imported and related to outbreaks in Europe and the USA. Therefore, it is necessary to continue monitoring outbreaks in Japan in conjunction with global epidemics.

Melanin-producing medullary thyroid carcinoma with transformation to melanoma: A case report.

Only one case of melanoma arising from melanin-producing medullary thyroid carcinoma (MTC) has been reported previously. In the present study, a second such case was reported and compared with the previous one. The patient was an 86-year-old male who presented with a right anterior neck mass. Ultrasound revealed a nodule measuring 49x48x40 mm in the right lobe of the thyroid. The levels of serum calcitonin (2,298 pg/ml) and carcinoembryonic antigen (CEA; 27.0 ng/ml) were markedly elevated. Aspiration cytology revealed suspected malignant anaplastic thyroid carcinoma and total thyroidectomy without neck nodal dissection was performed. On gross observation, the nodule was well encapsulated, soft, solid and black. Light microscopy indicated that the nodule was composed mainly of large, occasionally huge, pleomorphic cells with a solid or alveolar growth pattern. On immunohistochemistry, these cells were positive for melan-A and S-100 protein, and negative for thyroid transcription factor 1, calcitonin, chromogranin A and CEA. In the subcapsular area, melanin-producing MTC was intimately intermingled with the pleomorphic cells. No primary site of the melanoma was detectable in other organs. At three years after surgery, the patient died due to metastasis of the melanoma to the brain. The previously reported case had no detectable recurrence or distant metastasis up to 11 years after surgery. In comparison with that case, the present case had a similar morphology but the outcome was poorer. Thus, the prognosis of melanoma that transforms from MTC appears to remain uncertain.

A study of quality assessment in SARS-CoV-2 pathogen nucleic acid amplification tests performance; from the results of external quality assessment survey of clinical laboratories in the Tokyo Metropolitan Government external quality assessment program in 2020.

INTRODUCTION: The Tokyo Metropolitan Government (TMG) conducted an external quality assessment (EQA) survey of pathogen nucleic acid amplification tests (NAATs) as a TMG EQA program for SARS-CoV-2 for clinical laboratories in Tokyo. METHODS: We diluted and prepared a standard product manufactured by Company A to about 2,500 copies/mL to make a positive control and distribute it with a negative control. The participants reported the use of the NAATs methods for SARS-CoV-2, the name of the real-time RT-PCR kit, the name of the detection device, the target gene(s), nucleic acid extraction kit, Threshold Cycle value in the case of RT-PCR and the Threshold time value and Differential calculation value in the case of Loop-Mediated Isothermal Amplification (LAMP) method. RESULTS: As a result, 17 laboratories using fully automated equipment and 34 laboratories using the RT-PCR method reported generally appropriate results in this EQA survey. On the other hand, among the laboratories that adopted the LAMP method, there were a plurality of laboratories that judged positive samples to be negative. CONCLUSION: The false negative result is considered to be due to the fact that the amount of virus genome contained in the quality control reagent used this time was below the detection limit of the LAMP method combined with the rapid extraction reagent for influenza virus. On the other hand, false positive results are considered to be due to the non-specific reaction of the NAATs. The EQA program must be continued for the proper implementation of the pathogen NAATs.

Effectiveness and cost-effectiveness of influenza vaccination for elderly people.

For elderly people who have low incidence of influenza, calculation of credible vaccine effectiveness (VE) sometimes becomes difficult. Currently, VE for elderly people is insufficient to ascertain the precise efficacy specifically. Cost-effectiveness of influenza vaccination of elderly people is discussed widely in terms of topics and areas. This report describes research results demonstrating influenza vaccination effectiveness among elderly people based on recent findings. Newly available influenza vaccination for elderly people appears to be cost-effective compared with that of trivalent inactiveted influenza vaccine. Overall, for all influenza virus types, it remains unclear whether influenza vaccination shows high VE. A decreasing effect of repeated vaccination was confirmed partially by test negative design and a serological study of cohorts. However, some studies have found no such decreasing effect. Measurement of VE and subsequent analysis of the cost-effectiveness of influenza vaccination for elderly people requires long-term monitoring using serological studies and test negative design.

Evaluating Apple Inc Mobility Trend Data Related to the COVID-19 Outbreak in Japan: Statistical Analysis.

BACKGROUND: In Japan, as a countermeasure against the COVID-19 outbreak, both the national and local governments issued voluntary restrictions against going out from residences at the end of March 2020 in preference to the lockdowns instituted in European and North American countries. The effect of such measures can be studied with mobility data, such as data which is generated by counting the number of requests made to Apple Maps for directions in select countries/regions, sub-regions, and cities. OBJECTIVE: We investigate the associations of mobility data provided by Apple Inc and an estimate an an effective reproduction number R(t). METHODS: We regressed R(t) on a polynomial function of daily Apple data, estimated using the whole period, and analyzed subperiods delimited by March 10, 2020. RESULTS: In the estimation results, R(t) was 1.72 when voluntary restrictions against going out ceased and mobility reverted to a normal level. However, the critical level of reducing R(t) to <1 was obtained at 89.3% of normal mobility. CONCLUSIONS: We demonstrated that Apple mobility data are useful for short-term prediction of R(t). The results indicate that the number of trips should decrease by 10% until herd immunity is achieved and that higher voluntary restrictions against going out might not be necessary for avoiding a re-emergence of the outbreak.

Effects of voluntary event cancellation and school closure as countermeasures against COVID-19 outbreak in Japan.

BACKGROUND: To control the COVID-19 outbreak in Japan, sports and entertainment events were canceled and schools were closed throughout Japan from February 26 through March 19. That policy has been designated as voluntary event cancellation and school closure (VECSC). OBJECT: This study assesses VECSC effectiveness based on predicted outcomes. METHODS: A simple susceptible-infected-recovered model was applied to data of patients with symptoms in Japan during January 14 through March 26. The respective reproduction numbers for periods before VECSC (R0), during VECSC (Re), and after VECSC (Ra) were estimated. RESULTS: Results suggest R0 before VECSC as 2.534 [2.449, 2.598], Re during VECSC as 1.077 [0.948, 1.228], and Ra after VECSC as 4.455 [3.615, 5.255]. DISCUSSION AND CONCLUSION: Results demonstrated that VECSC can reduce COVID-19 infectiousness considerably, but after VECSC, the value of the reproduction number rose to exceed 4.0.

Risk factors affecting the failure to complete treatment for patients with latent tuberculosis infection in Tokyo, Japan.

OBJECTIVE: The treatment completion rate for all latent tuberculosis infection (LTBI) patients in Tokyo was 83.6% in 2014: somewhat lower than the targeted goal of 85%. This study examines the association between risk factors and LTBI patients' failure to complete treatment. METHODS: We collected data related to the treatment of LTBI patients who were reported to public health centers in Tokyo from January 2014 through December 2014. Data included potential risk factors affecting treatment, treatment results, and patient characteristics. We used Fisher's exact test to evaluate risk factors affecting failure to complete treatment. The failure rate was defined as the incompletion rate of treatment. RESULTS: Of 1060 notified cases, 877 had completed treatment; 116 had not completed treatment. Of these 116 cases, failure to complete treatment in 52 cases was attributable to side effects of anti-tuberculosis drugs. Reasons other than side effects were given for 64 cases. Another 67 cases could not be followed up. In all, 941 cases were analyzed, excluding cases lost to follow-up and cases for which patients had not completed treatment because of anti-tuberculosis drug side effects. Failure rates among foreign-born patients (26.9%) were significantly much higher than those among Japan-born patients (3.9%). Statistical tests indicated no presumed potential risk factor as significant. However, "no supporter for foreign-born LTBI patients" was marginally significant. CONCLUSION: Only "no supporter for foreign-born LTBI patients" was found to be marginally significant. More data must be accumulated to assess the risk factors affecting LTBI treatment.

Higher Incidence of Syphilis among Patients with HIV Infection: Population Study using Surveillance Data of Tokyo, Japan.

In Japan, the reported cases of syphilis have been increasing since 2011 especially in large cities such as Tokyo. The objective of this study was to evaluate the risk of HIV infection for syphilis co-infection on the population of Tokyo, Japan. We analyzed data of syphilis cases obtained from additional surveillance by the Tokyo Metropolitan Government in 2018, including those with human immunodeficiency virus (HIV) infection as well as data of HIV/acquired immunodeficiency syndrome (AIDS) cases during 1985-2017. We calculated the incidence of symptomatic syphilis cases among HIV-infected or non-HIV-infected individuals. Similarly, we calculated the incidence of syphilis, including asymptomatic cases, among each population. The relative risk of HIV infection for syphilis, including or excluding asymptomatic syphilis cases, was estimated. The relative risk was calculated by dividing the incidence of syphilis in the HIV-infected population by that in the non-HIV-infected population. Of the 1,775 syphilis cases reported in 2018, 172 cases were infected with HIV, 575 cases were uninfected, and the remainder were either unknown or not reported. The cumulative number of HIV/AIDS cases during 1985-2017 in Tokyo was 9,629; among them, 172 were co-infected with syphilis. The relative risk of HIV infection for syphilis was estimated as 423.29 if asymptomatic syphilis cases were included, and 372.37 if they were excluded. These results showed an extremely high risk of HIV infection. Since many syphilis cases have unknown or unreported HIV infection status, reduction of these cases might contribute to more reliable estimation of HIV infection risk.

Negative effect on immune response of repeated influenza vaccination and waning effectiveness in interseason for elderly people.

BACKGROUND: Through test negative designs for visiting a doctor because of influenza-like illness, many studies have found decreasing efficacy of repeated vaccination. Furthermore, waning effectiveness during interseason periods has been reported. This study was conducted to confirm negative effects of repeated vaccination in individuals with the same vaccine strain and to measure waning effects. METHODS: Our cohort includes 66 participants older than 65 years old recruited from an outpatient department of one hospital. All were vaccinated, with hemagglutination inhibition (HI) antibody titers measured from 2001/02 season through the 2003/04 season. HI antibody titers were measured three times in one season: pre-vaccination, post-vaccination, and post-epidemic. To test negative effects of immune response to the repeated vaccination, differences between protection rates and differences between response rates were analyzed for individuals in the two consecutive seasons. For the test of waning effectiveness, we measured the difference in geometric mean titers of HI antibody between post-epidemic results and pre-vaccination results obtained in the following season. RESULTS: Protection rates were 40-55% in A/New Caledonia/20/99 and ≥75% in A/Panama/2007/99 by repeated vaccination. In A/New Caledonia/20/99 and A/Panama/2007/99 in the 2003/04 season, significant decreases were found in protection rates from the earlier seasons, although the rate for A/Panama/2007/99 in the 2002/03 season increased significantly from that of the prior season. The respective response rates in the 2003/04 season in A/New Caledonia/20/99, and in the 2002/03 and 2003/04 seasons in A/Panama/2007/99 decreased significantly from those of earlier seasons. Regarding waning effectiveness, antibody titers for A/New Caledonia/20/99 in 2003/04 season, and A/Panama/2007/99 in 2002/03 and 2003/04 seasons decreased significantly to 37.0-66.7%. CONCLUSION: Results show significant negative effects of immune response by repeated vaccination and show significant waning effectiveness during the interseason for individuals with the same strain of influenza type A. The proportion of elderly people with HI antibody titers of ≥1:40 might be maintained by repeated influenza vaccination.

Syndromic surveillance using ambulance transfer data in Tokyo, Japan.

Bioterrorism attacks become more probable when important high-profile international or political events are held, such as G7 summit meetings or mass gathering events including Olympic and Paralympic games and FIFA World Cup tournaments. Outbreaks of infectious disease and widespread incidents of food poisoning are also public health concerns at such times. In Japan, the Tokyo Metropolitan Government operates Ambulance Transfer Syndromic Surveillance (ATSS), which can help monitor such incidents. The present study presents and assesses the ATSS framework. During the study period of October 2017 through November 2018, we monitored 33 areas for symptoms of 9 categories: vomiting/nausea, dizziness, palpitation, unconsciousness, breathing disorder, fever, spasm/paralysis, collapse/weakness, and bloody emesis/nasal hemorrhage. Among all symptoms, we found 9929 low-level aberrations, 2537 medium-level aberrations, and 577 high-level aberrations, with respective frequencies of 9.2%, 2.3%, and 0.5%. Of those, Tokyo Metropolitan Institute of Public Health reported the information to Tokyo Metropolitan Government 28 times during the period. Of the 28 identified clusters, Tokyo Metropolitan Government judged the necessity for investigating 7. All of those were investigated at hospitals by the jurisdictional public health center. Because ATSS covers almost the entire Tokyo metropolitan area, with about 13.8 million residents, it is definitely the largest syndromic surveillance in the world.

Determinants of Vaccination Coverage for the Second Dose of Measles-Rubella Vaccine in Tokyo, Japan.

In Japan, some measles outbreaks were initiated by a tourist from oversea and foreign workers recently. Moreover, rubella outbreak emerged since July 2018 mainly in the South Kanto, and the outbreak is currently ongoing in 2019. It is important to maintain a high measles-rubella combined vaccine (MR) coverage for measles-rubella control. Vaccination coverage for the second dose of MR (MR2) is 90.8% in Tokyo in 2016, which was the third worst among all prefectures in Japan. The purpose of this study was to clarify determinant factors of vaccination coverage for MR2 in Tokyo. Data were obtained for 49 wards and cities in Tokyo in 2016. We regressed vaccination coverage of MR2 on the times of notification by mail, the proportion of households receiving welfare payments, and the proportion of non-Japanese elementary school students. In addition to the simplest specification, five factors were included separately as explanatory variables: the proportion of public health nurses; the ratio of the number of pediatric medical facilities to the number of preschool and elementary school children; the moving-in rate; the proportion of households with a single parent; and the proportion of households with husband and wife both working. Results show that a high proportion of households receiving welfare payments, notification by two or more letters, and moving-in rate or a lower proportion of non-Japanese elementary school students improve coverage. In conclusion, the health authorities can exert efforts to reduce burden of time spent for vaccination and provide sufficient information to improve coverage.

Rapid increase of syphilis in Tokyo: an analysis of infectious disease surveillance data from 2007 to 2016.

The objective of this study was to examine the trends of primary and secondary syphilis in Tokyo between 2007 and 2016 using national infectious disease surveillance data. We analysed all 3269 cases reported during these 10 years. A statistically significant increase in cases was observed after 2010 with a more rapid rate of increase after 2014 mainly in urban areas in Tokyo. The notification rates per 100 000 population in 2010, 2014 and 2016 were 0.9 (n = 113), 2.2 (n = 295) and 8.7 (n = 1190), respectively. Domestic syphilis transmission was suspected in 92.6-99.3% of cases during the period 2007-2016. Until 2013, the increase was mainly observed among men who have sex with men (MSM); however, heterosexual transmission became more dominant and eventually surpassed transmission among MSM in 2015. In 2016, the notified cases of infections through heterosexual contact were 22.3 and 40.4 times higher in men and women, respectively, compared to those in 2010. The median ages of affected heterosexual men and women were 37 (interquartile range: 28-46) and 26 (interquartile range: 22-32) years, respectively. Reports of oropharyngeal lesions have been increasing among both men and women with syphilis. The number of congenital syphilis cases reported in Tokyo was 0 to 3 cases per year during the study period. More information and further analysis are needed to explain the reason for this increase.

Association of influenza outbreak in each nursery school and community in a ward in Tokyo, Japan.

In nursery schools, influenza outbreaks have occurred every year. However, influenza characteristics of its diffusion among nursery schools, within each nursery school, and among classes of different ages in nursery schools remains unclear. This paper presents an examination of these matters using the Nursery School Absenteeism Surveillance System (NSASSy). All nursery schools in ward A in Tokyo introduced to the NSASSy in 2015. The study period was November 2015 through March 2016. The data of influenza patients were extracted from NSASSy. We examined four definitions of 'starting date of community outbreak' (SDCO) of influenza: 1) the first recorded day of influenza patients (SDCO1), 2) the last day of influenza patients recorded for two consecutive days (SDCO2), 3) three consecutive days (SDCO3), and 4) four consecutive days (SDCO4). We evaluated those four definitions by duration of the initial case at each nursery school from SDCO and evaluated the proportion of nursery schools at which the initial case occurred before SDCO. The average durations of initial cases at respective nursery schools from SDCO1-4 were 40.3, 26.3, 23.1 and 13.3 days. The respective proportions of nursery schools at which the initial case occurred before SDCO1-4 were 3.1%, 6.4%, 9.4% and 40.6%. Results demonstrate that SDCO3 is an appropriate definition of SDCO. Robustness checks for other areas, seasons, and population size constitute the next challenge for research in this area.

Enhancing Preparedness against Rubella at the Workplace: Proactive Prevention Efforts by the Tokyo Metropolitan Government.

In the 2012-2013 rubella epidemic in Japan, most transmissions in Tokyo occurred at workplaces, especially among men aged 20-49 years. This tendency was likely related to previous rubella immunization policies that prioritized female adolescents. Since 2015, the Tokyo Metropolitan Government has been promoting a project to prevent rubella and other infectious diseases in workplaces. Companies participate by choosing one or more of three options: (i) acquire fundamental understanding of infectious diseases, (ii) develop a Business Continuity Plan (BCP) for infectious diseases in the workplace, and (iii) increase rubella antibody prevalence in employees.Criteria for accomplishment are (i) at least 80% of employees complete the infectious disease training modules or (ii) produce a BCP and (iii) at least 90% of employees demonstrate the presence of antibodies at levels sufficient for preventing rubella. As of July 2018, 39.8% (n ＝ 90) of the 226 companies that began participating in 2015-2017 had met at least one accomplishment criteria (Option I, 42.7% of 192 companies; Option II, 19.3% of 140; and Option III, 17.0% of 53). The main project challenges were recruiting companies and following participating companies. Although early in its implementation, this project has made considerable contributions toward rubella elimination in Japan.

Shedding of Rubella Virus among Infants with Congenital Rubella Syndrome Born in Tokyo, Japan, 2013-2014.

Rubella is usually a mild illness, with febrile rash being its main symptom. However, serious consequences of rubella infection can result when the infection occurs during the early stages of pregnancy. After the occurrence of a rubella outbreak in Japan that was observed from 2012 to 2013, 45 infants were reportedly born with congenital rubella syndrome (CRS). We prospectively followed the 15 CRS cases reported in Tokyo to determine the virus shedding periods by using nested reverse transcriptase-polymerase chain reaction to detect rubella virus genes. Throast swabs were used for virus detection. The virus shedding period was measured from birth until the time when the sample last tested positive followed by 2 consecutive negative samples. Kaplan-Meier method was used to estimate the proportion of cases remaining positive for rubella virus genes over time. The proportion of CRS cases shedding virus dropped steadily after birth, dropping to 33.8% at 6 months and 16.9% at 12 months. Our findings also suggested that the earlier the mother's onset of rubella during pregnancy, the longer the infant remained positive. Based on our findings, we believe that infants with CRS should be monitored for rubella virus shedding until 1 year of age.

Increase in Primary and Secondary Syphilis Notifications in Men in Tokyo, 2007-2013.

The number of notified syphilis cases in Tokyo has more than doubled in recent years. The number of reported primary and secondary syphilis cases increased from 108 cases (0.8 per 100,000 population) in 2007 to 245 cases in 2013 (1.9 per 100,000 population). During this period, the majority of cases was male (905/1,024), and the recent increase among primary and secondary syphilis cases was attributed to the increase among males (90/108 [83%] cases in 2007 to 218/245 [89%] cases in 2013); men aged 20-49 years contributed most to the increase, with those aged 30-34 years having the highest notification rate in 2013. Male-to-male transmission was the primary route of infection reported, and men who have sex with men (MSM) accounted for nearly 80% of male cases in 2013. Syphilis appears to be reemerging in Tokyo, and reducing the risk of acquiring syphilis among MSM aged 20-49 years should be a public health priority in Tokyo.

Radioactive iodine (RAI) therapy for distantly metastatic differentiated thyroid cancer (DTC) in juvenile versus adult patients.

In general, juvenile differentiated thyroid carcinoma (DTC) demonstrate indolent characteristics and favorable prognosis are observed in comparison with many other carcinomas. However, recurrence is frequent, necessitating additional treatment, including radioactive iodine (RAI) therapy. In this report, the probability of recurrence, prognostic factors, treatment, and outcomes in both juvenile- and adult-onset DTC were analyzed and compared. At our institution, a total of 1552 DTC patients underwent thyroidectomy and/or lymph node dissection. The patients included 23 in their teens, 118 in their twenties, and 1412 in their thirties or older. The risk factors for distant metastases for DTC were male gender, follicular carcinoma, size of the PTC primary tumor, cervical lymph node metastases from PTC, and the presence of more than two distant metastatic foci. Patients with the highest risk underwent RAI ablation in line with institutional guidelines. Although the overall outcome in our juvenile patients was excellent, during follow-up, 4 (17.4%) of the 23 patients developed recurrent disease: 91.3% achieved complete remission, 4.35% partial remission, and 4.35% stable disease, with no disease-related deaths. Among the 118 patients in their twenties to thirties, 1 (0.8%) experienced progressive disease and disease-related death. A younger age at diagnosis and less radical primary surgery without subsequent RAI ablation are factors strongly predictive of distant metastases in patients with juvenile-onset DTC. To reduce the rate of relapse and improve surveillance for recurrent disease, total thyroidectomy followed by RAI appears to be the most beneficial initial treatment for patients with high- and intermediate-risk juvenile DTC.

Telomere shortening in breast cancer correlates with the pathological features of tumor progression.

Telomeres are involved in the maintenance of genomic stability. Telomere alteration has been observed in most human cancer types, and is known to be a feature of malignancy. The aim of the present study was to evaluate whether the telomere length of breast cancer cells correlates with TNM stage and several pathological features. We investigated a total of 44 breast cancers, including 17 scirrhous, 15 papillotubular and 12 solid-tubular carcinomas. Telomere lengths were determined by tissue quantitative fluorescence in situ hybridization (Q-FISH), and compared according to the TNM stage, histological tumor size, lymph node metastases, vascular invasion and immunohistochemical status (ER, PR, HER2 status and Ki67 labeling index). In all histological types, telomeres of cancer cells were significantly shorter than those of normal epithelial cells. Mean telomere length was significantly less in patients with TNM stage III, and in those with large tumors, lymph node metastases and vascular invasion. Our results suggest that the telomere length of cancer cells is strongly correlated with the degree of cancer progression.