Invasive Cancer Group Research Articles

The differential diagnosis of lung precursor glandular lesions, micro-invasive adenocarcinoma, and invasive adenocarcinoma using low dose spectral computed tomography perfusion imaging.

Few studies about the association between computed tomography (CT) perfusion imaging parameters and invasiveness in lung adenocarcinoma (LUAD) have been conducted using low dose spectral CT perfusion imaging. The purpose of this study was to investigate application of spectral revolution CT low-dose perfusion imaging in the differential diagnosis of different pathological subtypes of LUAD. This was a cross-sectional study based on historical data from January 2018 to May 2019 in Peking University Cancer Hospital & Institute. A total of 62 cases were enrolled, including 2 cases of atypical adenomatous hyperplasia (AAH), 3 cases of adenocarcinoma in situ (AIS), 4 cases of minimally invasive adenocarcinoma (MIA), and 53 cases of invasive adenocarcinoma (IAC), all confirmed with pathology. The inclusion and exclusion criteria were regulated. Using Revolution low-dose CT perfusion imaging (GE, USA), the CT perfusion parameters of hemodynamics were obtained: blood flow (BF), blood volume (BV), impulse residue function time of arrival (IRF TO), maximum slope of increase (MSI), mean transit time (MTT), permeability surface area product (PS), positive enhancement integral (PEI), and maximum enhancement time (Tmax). Univariate analysis of variance (ANOVA) or Kruskal-Wallis test was used to compare the differences of CT perfusion quantitative parameters among AAH, AIS, MIA, and IAC. Mann-Whitney test was used to compare the difference of CT perfusion imaging parameters between preinvasive lesions (AAH and AIS) and invasive lung cancer (MIA and IAC). Statistically significant differences in IRF TO were observed in LUAD with different invasiveness, namely, among AIS, MIA, and IAC groups (0.56±0.74 vs. 0.54±1.08 vs. 4.39±2.19, P=0.004). Statistically significant differences in IRF TO were also observed between pre-invasive lesions group (AAH and AIS) and invasive lung cancer group (MIA and IAC) (1.12±1.27 vs. 3.75±2.79, P=0.031), and between AAH + AIS + MIA groups and IAC group (0.83±1.13 vs. 4.12±2.69, P<0.001). There were no statistically significant differences in other CT perfusion parameters of hemodynamics among different pathological subtypes of LUAD (P>0.05). The low-dose perfusion parameter IRF TO of revolution CT has the potential to be employed in the differential diagnosis of different pathological subtypes of LUAD.

Pancreatic ductal adenocarcinomas concomitant with intraductal papillary mucinous neoplasms of the pancreas: A investigation of those clinicopathological features by analyzing 48 patients who underwent surgery for those lesions

BackgroundDifferences between pancreatic ductal adenocarcinomas (PDACs) concomitant with intraductal papillary mucinous neoplasm (IPMN) (C-PDACs), those without IPMN (NC-PDACs) and invasive cancers derived from IPMN (IC-Ds) have not been fully clarified. MethodsForty-eight patients with C-PDAC were included to investigate the differences in 1) clinicopathological features and 2) post-operative courses among the three invasive cancer groups. Results1) Characteristics of C-PDACs were mostly similar to those of NC-PDACs; whereas, between C-PDACs and IC-Ds, the rate of mucinous carcinoma (2%/25%, p = 0.003) and pathological stage (IA, 15%/36%, p = 0.033; III, 31%/4%, p = 0.015) significantly differed. Most C-PDACs coexisted with small, multifocal IPMNs without mural nodules. 2) Cumulative 5-year recurrence-free survival (RFS) rate related to extra-pancreatic recurrence was significantly worse in C-PDACs than in IC-Ds (35%/69%, p = 0.008) and was not significantly different between C-PDACs and NC-PDACs (35%/18%). This related to intra-pancreatic recurrence tended to be poor in the order of IC-Ds, C-PDACs, and NC-PDACs (69%/82%/93%). ConclusionsBecause characteristics of IPMNs remarkably differed between C-PDACs and IC-Ds, another algorithm specific to the early detection of C-PDACs is necessary. Appropriate post-operative managements according to the two types of recurrences may contribute to the improvement in the prognoses of C-PDACs/IC-Ds.

Long-term (10-year) outcomes and prognostic factors in resected intraductal papillary mucinous neoplasm tumors in Finland: A nationwide retrospective study

BackgroundThe degree of dysplasia is the most important prognostic factor for patients with resected intraductal papillary mucinous neoplasms. Intraductal papillary mucinous neoplasms are predominantly premalignant conditions; in most cases, surveillance is an adequate treatment. If worrisome features are present, surgery should be considered. However, there is limited data on the long-term prognosis of resected intraductal papillary mucinous neoplasms. We aimed to ascertain the nationwide survival of patients with resected intraductal papillary mucinous neoplasms and identify factors associated with survival. MethodsThis is a retrospective nationwide cohort study. All intraductal papillary mucinous neoplasms operated on in Finland between 2000 and 2008 were identified. Patient records were evaluated, and original radiologic data and histologic samples were re-evaluated. Survival data were collected after a 10-year follow-up period. ResultsOut of 2,024 pancreatic resections, 88 were performed for intraductal papillary mucinous neoplasm. The median age of the patients was 65 years. Histologic diagnoses were main duct intraductal papillary mucinous neoplasm 47/88 (53,4%), mixed-type intraductal papillary mucinous neoplasm 27/88 (30.7%), and branchduct intraductal papillary mucinous neoplasm 14/88 (15.9%). Of the tumors, 40/88 (45.5%) were low-grade dysplasia, 9/88 (10.2%) high-grade, and 39/88 (44.3%) were invasive cancer. The median survival was 121 (range 0–252) months. Ten-year survival was 72.5%, 66.7%, and 23.1% in the low-grade dysplasia, high-grade dysplasia, invasive cancer groups, respectively. Ten-year mortality for pancreatic cancer was 5%, 9.1%, and 71.8% in the low-grade dysplasia, high-grade dysplasia, invasive cancer groups, respectively. ConclusionOverall, 44.3% of the patients had a malignant tumor, and three-quarters (74.5%) of the main duct intraductal papillary mucinous neoplasms were malignant or high-grade dysplasia at the time of surgery. Ten-year survival was significantly better in patients operated on at the stage of a premalignant tumor (low-grade dysplasia + high-grade dysplasia) than in patients operated on at the stage of a malignant tumor.

Significant impact of a history of prior or concomitant upper urinary tract cancer on the recurrence and progression of non-muscle invasive bladder cancer.

The objective of the present study was to evaluate the prognostic impact of the upper urinary tract cancer status on recurrence-free survival and progression-free survival, and to develop risk stratification systems that include the upper urinary tract cancer status for patients with non-muscle invasive bladder cancer. The present study included 40 (upper urinary tract cancer-non-muscle invasive bladder cancer group) and 285 (non-muscle invasive bladder cancer alone group) patients with and without a history of prior or concomitant upper urinary tract cancer, respectively. Nine clinicopathological findings between the two groups were compared, and risk stratification systems for the recurrence and progression of non-muscle invasive bladder cancer were developed. Recurrence-free survival and progression-free survival in the upper urinary tract cancer-non-muscle invasive bladder cancer group were significantly inferior to those in the NMIBC alone group (P<0.001 and P=0.006, respectively). Multivariate analyses identified the following independent prognosticators: multiplicity and upper urinary tract cancer status for recurrence-free survival, and pT category and upper urinary tract cancer status for progression-free survival. Significant differences were noted by the risk stratification systems based on the positive number of independent predictors of recurrence-free survival and progression-free survival (P<0.001 and P=0.007, respectively). The concordance indices of recurrence-free survival were 0.627, 0.588 and 0.499 in this study stratification, EORTC risk table and CUETO model, respectively. Those of progression-free survival were 0.752, 0.740 and 0.714, respectively. The present results suggest the significant impact of a history of prior or concomitant UUTC on recurrence-free survival and progression-free survival in non-muscle invasive bladder cancer patients, and risk stratification systems that include the upper urinary tract cancer status for the recurrence and progression of non-muscle invasive bladder cancer are promising tools for predicting the outcomes of these patients.

Endoscopic submucosal dissection for rectal neoplastic lesions: experience from a European center.

IntroductionNowadays, various endoscopic resections including polypectomy, endoscopic mucosal resection (EMR), and endoscopic submucosal dissection (ESD) are well known first-line approaches for early neoplastic rectal tumors.Material and methodsIn this case series study, we analyzed 320 ESD procedures performed in a high-volume colorectal center in Poland, Europe. The aim of this study was to retrospectively evaluate ESD procedure in cases of rectal carcinoma performed by a single trained operator in a referral center provided with endoscopy.ResultsOverall, en bloc resection was observed in 92.5% of patients (296/320). The en bloc resection rate was at a similar level in those lesions with involved anal sphincters versus tumors without involvement (93.85% vs. 92.16%; p=0.644). R0 resection was noted in 89.4% of patients (286/320). The overall curative ESD rate was 85.94% (n=275). The curative ESD rate in the invasive cancer group reached 52.6% (n=20). We observed ESD-related adverse events, such as bleeding and perforation, in 3.4 % of patients (n=11).ConclusionsWe have demonstrated that ESD in rectal tumors is an efficient and safe procedure with a high curative rate, even in difficult lesions. Anal sphincter localization and recurrent character of the lesion have no impact on the final outcomes. The ESD approach should have been considered for all rectal tumors, especially those lesions suspected of superficial mucosal invasion, as it can serve as a staging method and may have been curative for adenomas and cancers limited to mucosa.

MicroRNA Levels in Cervical Cancer Samples and Relationship with Lesion Grade and HPV Infection.

miR-21, miR-214 and miR-let-7a are three validated and well-known miRNAs. miR-21 is described as an "oncomir" while miR-214 and miR-let-7a are described mainly as tumor suppressors. The role of these miRNAs remains unclear in cervical cancer, an important malignancy among women worldwide and responsible for many deaths every year. The objective of this study is to describe the expression profile of miR-21, miR-214 and miR-let-7a in plasma and in cervical scraping from a control group and patients with different grades of cervical lesions and invasive cervical cancer and correlate with HPV infection groups. Plasma and cervical scraping were submitted to DNA and RNA extraction. HPV detection and typing were performed by conventional PCR followed by PAGE to amplicons interpretation. The miRNA relative expression in plasma and cervical scraping samples was performed by real time PCR using specific TaqMan probes. miR-21 (p=0.0277) and miR-214 (p=0.0151) were up-regulated in cervical scraping samples of invasive cervical cancer (ICC) group. However, miR-214 was also up-regulated in the LSIL group (p=0.0062). Both miRNAs were not related to HPV infection. However, miR-let-7a was higher in HPV positive plasma samples (p=0.0433) than in HPV negative plasma samples and the correlation analysis confirmed the association between the levels of this miRNA with the presence of HPV (p=0.0407; r=0.3029), but not with lesion grade (p>0.05). Our results suggest that miR-21 is related to cervical cancer progression and miR-214 appears to have an ambiguous role in cervical lesions. miR-let-7a may be upregulated at a systemic level in patients with HPV infection.

MiR-25 and KLF4 relationship has early prognostic significance in the development of cervical cancer

Cervical squamous cell carcinoma (SCC) is one of the common cancer types among women. MicroRNAs (miRNAs) are small non-coding RNAs that play an important role in the formation and development of many cancer types by regulating expression of their targets. While many studies have investigated the relationship between miRNAs and cervical cancer, no robust miRNA biomarkers have been defined yet for diagnosis of cervical lesions.In this study, we performed a statistical meta-analysis to identify miRNAs and a class compassion analysis to evaluate mRNAs with the power to discriminate between normal, intraepithelial lesions and invasive cancer samples. Differentially expressed (DE) mRNAs were compared with the targets of meta-miRNAs. After bioinfomatics analysis and qRT-PCR validations with cytology samples and FFPE tissues, we defined miR-25 and its target KLF4 (Kruppel-like factor 4) as candidate biomarkers for in vitro studies. Our results showed that miR-25 expression was significantly higher in precancerous lesions and invasive carcinoma while presenting consistent expression patterns in both cytological and FFPE tissue samples. In line with this, its direct target KLF4 expression decreased in precancerous lesions in cytological samples and also in the invasive cancer group in FFPE tissues. Furthermore, in vitro studies showed that mir-25 inhibition decreased proliferation and motility of HeLa cells and promoted an increase in the protein level of KLF4. We conclude that inhibition of miR-25 may upregulate KLF4 expression and regulate cell proliferation and motility in cervical cancer.

The usefulness of ultrafast MRI evaluation for predicting histologic upgrade of ductal carcinoma in situ

PurposeThe purpose of this study was to investigate the usefulness of ultrafast MRI with conventional dynamic contrast-enhanced (DCE)-MRI for predicting histologic upgrade of ductal carcinoma in situ (DCIS) to invasive cancer. MethodsThis retrospective study enrolled 53 biopsy-proven DCIS lesions in 53 patients and divided into two groups based on postoperative histopathologic diagnoses: non-upgrade and upgrade to invasive cancer groups. Imaging features of conventional DCE-MRI and ultrafast MRI, and histopathologic features were reviewed and compared between the two groups. Interobserver agreements for MRI features were analyzed by two radiologists. The radiologic and histopathologic parameters for predicting histologic upgrade of DCIS were identified using multiple linear regression. ResultsSeventeen lesions (32.1 %) were histologically upgraded to invasive cancer after surgery. The interobserver agreement for ultrafast MRI parameters was excellent, and maximum slope (MS) and maximum enhancement (ME) showed the highest reliability (intraclass correlation coefficients, 0.907 and 0.897, respectively). The upgrade group showed significantly larger lesion size on MRI (median 40 mm [25th to 75th percentiles 16.0–83.0] vs. 18.5 mm [10.0−29.8], p < 0.001), higher MS (12.1 %/s [8.2−13.9] vs. 8.7 %/s [6.4−11.1], p = 0.004), and higher ME (236.5 % [153.7−253.7] vs. 175.4 % [140.1−207.7], p = 0.027) than non-upgrade group. Lesion size (≥ 20 mm), MS (> 11.5 %), and ME (> 229.1 %) were significant predictors for histologic upgrade, which could predict 10 cases of histologic upgrade (10/17, 58.8 %) without a false-positive case. ConclusionPreoperative ultrafast MRI with conventional DCE-MRI could be useful in management decisions for DCIS patients.

Real time quantitative methylation detection of PAX1 gene in cervical cancer screening

IntroductionDNA methylation is currently found to be associated with the progression of cervical intraepithelial neoplasia and the development of cervical cancer. The aim of this study was to analyze the...

Risk stratification of advanced colorectal neoplasia after baseline colonoscopy: Cohort study of 17 Japanese community practices.

Background and AimIn Japan, risk stratification after baseline colonoscopy is not widely accepted. We investigated the findings of baseline colonoscopies at 17 community practices and evaluated the risk of the incidence of advanced neoplasia over a 5‐year period.MethodsThis retrospective cohort study enrolled 3115 subjects over 40 years of age who underwent baseline colonoscopies and had at least one repeated colonoscopy within 5 years. Each group was classified based on the endoscopic findings of the baseline colonoscopy: no neoplasia/diminutive polyp <5 mm (N/D); small adenoma <10 mm; advanced adenoma; invasive cancer, respectively. We examined the incidence of advanced neoplasia during these 5 years and investigated the relationship between the surveillance colonoscopy and newly detected advanced neoplasia.ResultsThe small adenoma group did not show any significant increased risk as compared to the N/D group (hazard ratio [HR]: 0.799. 95% CI 0.442–1.443). There was a significantly increased risk in the advanced adenoma and invasive cancer groups (HR: 4.996, 95% CI 2.940–8.491, HR: 3.737, 95% CI 1.309–10.666). Cancer incidences during the study period were 0.18% in the N/D group, and 1.9% in the invasive cancer group, respectively. Undergoing surveillance colonoscopies twice within 5 years decreased the risk of advanced neoplasia.ConclusionsThere was a close relationship between the endoscopic findings of baseline colonoscopies and subsequent advanced neoplasia development. Risk stratification for advanced neoplasia based on the baseline findings can serve as a useful index for determining the optimal interval and frequency of colonoscopies over a 5‐year period.

Human papillomavirus and human telomerase RNA component gene in cervical cancer progression

This study aimed to examine hTERC gene in different grades of cervical intraepithelial neoplasia (CIN) and cervical cancer, and the association between hTERC and high risk-human papillomavirus (HR-HPV) infection. Patients who underwent cervical cancer screening at the Second Affiliated Hospital of Kunming Medical University between October 2010 and December 2011 were enrolled. All patients underwent liquid-based cytology test and hybrid capture 2 (HC2) for HPV detection. hTERC was examined using fluorescence in situ hybridization (FISH). Cervical colposcopy biopsy was performed if any of the three results was positive. HC2, FISH, and pathology were compared. A total of 1200 women underwent screening, 150 patients underwent cervical biopsy: 32 in the normal group, 38 in the CIN1 group, 66 in the CIN2/3 group, and 14 in the invasive cervical cancer group. More patients had HR-HPV infection in the CIN2/3 group and ICC group compared with the CIN1 group. hTERC increased with increasing histological dysplasia. There was significant difference in hTERC positive rate between each of the three groups. More patients with hTERC gene amplification were observed in the positive HR-HPV group than in the HR-HPV negative group. In conclusion, hTERC is a potential marker for precancerous cervical cancer lesions. hTERC might be correlated with HR-HPV infection in cervical diseases.

Microbiota profile is different for early and invasive colorectal cancer and is consistent throughout the colon.

Microbiota have been associated with several diseases including colorectal cancer (CRC). This study aimed to evaluate the microbiota in early/invasive CRC utilizing stool and cytological brushes to determine differences in relative abundance (RA). Colonoscopy patients referred for endoscopic submucosal dissection or previous to CRC surgery were prospectively enrolled. Stool was collected pre-bowel preparation; and brush samples were taken during colonoscopy (three regions). DNA extraction, 16S rRNA next generation sequencing, and biostatistics (qiime and stamp software packages) followed. Primary outcome was the difference in RA of the Fusobacterium genus between the groups. Secondary outcomes included analyses of other microbiota. Twenty-five patients were included, of which 14 had invasive cancer (≥1000mm into the submucosa). The three major genera for invasive cancer were Bacterioides, Oribacterium, and Fusobacterium, whereas for early cancer were Oribacterium, Bacterioides, and Prevotella (decreasing order of RA). There was a significantly higher RA of Fusobacterium in the invasive cancer group (9.65% vs 0.95%, respectively, P<0.001). The RA of all genera was similar throughout the colon. In addition to Fusobacterium, the genera Corynebacterium, Enterococcus, Neisseria, Porphyromonas, and Sclegelella showed statistically higher RA in the invasive cancer group. Conversely, the genera Oribacterium, Desulfovibrio, Clostridiales, and Lactobacillus showed lower RA in the invasive cancer group. The RA of Fusobacterium is higher with invasive CRC than in early CRC patients. In addition, five other bacteria genera were found to be increased, and four decreased in invasive CRC patients. The microbiota per patient was similar throughout the colon.

Microvascular density and hypoxia-inducible factor in intraepithelial vocal fold lesions

ObjectiveThe promotion of neovascularisation is a crucial aspect of carcinogenesis. The study evaluates the microvascular density (MVD) and expression of hypoxia-induced factor (HIF-1α) in hypertrophic vocal fold (VF) lesions of different histopathological states including non-dysplastic, low-grade, high-grade dysplasia and invasive glottic cancer.Materials and methodsHistological specimens collected from patients diagnosed and treated in a single centre with different histological grades were immunohistochemically stained with CD31, CD34 and HIF-1α. Of the total number of 77 analysed VF specimens, 20 were non-dysplastic, 20 had low-grade dysplasia, 17 high-grade dysplasia and 20 were invasive cancers.ResultsThe highest mean value for MVD evaluated with expression of CD31 (MVD CD31) was 21.23 ± 14.46 and identified in the low-grade dysplasia group. The average MVD CD31 was 13.74 ± 5.56 and 20.11 ± 9.28 in the high-grade dysplasia and invasive cancer group, respectively. The highest MVD evaluated with CD34 (MVD CD34) was revealed for invasive cancer 35.64 ± 17.21. The MVD CD34 was higher for low-grade than in high-grade dysplasia (25.87 ± 12.30 vs 24.65 ± 15.92, respectively). The expression of HIF-1α was strong or very strong in 60% of non-dysplastic lesions, 100% of low-grade dysplasia cases, 53% of high-grade dysplasia cases and 50% of invasive cancer cases. The comparison of MVD CD31 with MVD CD34 revealed a strong positive correlation (ρ value 0.727). The comparison of both MVD CD31 and MVD CD34 with HIF-1α resulted in no linear relationship (ρ value of 0.143 and 0.165, respectively).ConclusionThe stage of low-grade dysplasia in intraepithelial vocal fold lesions is related to significant advancement of angiogenesis together with the highest hypoxia level.

An Updated Nomogram for Predicting Invasiveness in Preoperative Ductal Carcinoma In Situ of the Breast.

PurposeTo validate and update a nomogram for predicting ductal carcinoma in situ (DCIS) upstaging in preoperative biopsy.Materials and MethodsMedical records of 444 preoperative DCIS patients were evaluated and used to validate a previous version of the Severance nomogram for predicting DCIS upstaging in preoperative biopsy. Patients were divided into two groups according to the final postoperative pathology. Univariate and multivariate analyses with the chi-square test, Student's t-test, and binary logistic regression method identified new significant variables. The updated nomogram was evaluated with the C-index and Hosmer—Lemeshow goodness of fit test.ResultsThe area under a receiver operating characteristic curve for comparison with the previous nomogram was 0.48. In postoperative pathology, the pure DCIS and invasive cancer groups comprised 345 and 99 cases, respectively. Approximately 22.3% of patients preoperatively diagnosed with DCIS were upstaged to invasive cancer. Significant variables in the univariate analysis were operation type, human epidermal growth factor receptor 2 overexpression, comedo necrosis, sonographic mass, mammographic mass, preoperative biopsy method, and suspicious microinvasion in preoperative biopsy. In multivariate analysis, operation type, sonographic mass, mammographic mass, and suspicious microinvasion were risk factors for upstaging. The updated model with these variables showed moderate discrimination and was appropriate in the calibration test.ConclusionThe previous nomogram did not effectively discriminate upstaging of preoperative DCIS in an independent cohort. An updated version of the nomogram appears to provide more accurate information for predicting preoperative DCIS upstaging.

Can Selective Image-Guided Intraoperative Margin Resection Improve Re-Excision Rates after Lumpectomy in Ductal Carcinoma In Situ of the Breast?

The rate of positive margins after breast conserving surgery (BCS) can be as high as 50 per cent, and optimal techniques for reducing rates of positive margins are presently debated. Our institution has previously demonstrated low rates of margin re-excision using a standardized approach to intraoperative selective margin excision for patients undergoing BCS. We hypothesized that this approach can be used for patients with ductal carcinoma In Situ (DCIS) and can yield similar rates when compared with invasive cancer. We performed a retrospective analysis of women with breast cancer who underwent BCS from January 2012 through July 2016 using our institution's standardized approach to selective margin resection. Of the 152 patients who underwent BCS, there were 30 (20%) with DCIS and 122 (80%) with invasive cancer. There was no statistically significant difference in re-excision rates for DCIS (13.3%) and invasive cancer (13.1%). Notably, the DCIS group had a larger mean lesion size (P = 0.00009); however, the lesion was visible on ultrasound more often in the invasive cancer group (P = 0.007). This standardized approach to intraoperative selective margin excision can produce similar rates of margin re-excision for DCIS and invasive cancer and may be a viable option for lowering re-excision rates for patients with DCIS.

Abstract 4616: Cancer-associated MUC1 epitope-recognizing antibody as a novel immunohistochemical marker for breast carcinoma

Abstract Background: MUC1 has been used in clinical practice as a serum tumor marker (CA15-3) for monitoring recurrence and response to the treatment of breast cancers. However, it is not so practical to use the conventional anti-MUC1 antibody (C-Ab) for the differential diagnoses among malignant and benign tumors, because of its limited specificity to cancer-associated sugar chain structures. Recently, a novel epitope-defined (ED) antibody, which specifically recognizes MUC1 with cancer-associated carbohydrate antigens including Tn and sialyl-T antigens, was developed by our collaborators. In the present work, we focused on this Tn antigen-recognizing ED antibody (Tn-ED Ab) for MUC1, and examined the potential utility of this novel antibody as an immunohistochemical diagnostic marker of the breast.Design: Tissue microarray (TMA) consisting of invasive lesions and their non-neoplastic counterparts were constructed from 169 lesions of 167 individuals with invasive breast carcinomas (including 2 bilateral cases) resected and diagnosed at Hokkaido University Hospital from 2000 to 2003. We compared MUC1 immunoreactivity of Tn-ED Ab (clone SN-102) to commercially available C-Ab (clone Ma552) using TMA to evaluate its diagnostic performance and to analyze the association with clinicopathologic factors. Results: In invasive cancer parts, the immunoreactive positivity of Tn-ED Ab was observed predominantly in the cytoplasm (146/169) rather than in the cell membrane (5/169). The positive reaction of C-Ab was found in the cytoplasm and the membrane as well (156/169 and 93/169). Tn-ED Ab showed a lower expression rate in non-neoplastic parts and a high specificity in invasive cancer parts. Sensitivity/specificity in invasive parts was 86%/92% for Tn-ED Ab and 92%/47% for C-Ab. Moreover, the invasive cancer group with Tn-ED-positivity was significantly correlated with their molecular subtypes, low Ki-67 indices, and high ages, compared to those with Tn-ED-negativity (p=0.008, p=0.010 and p=0.027, respectively). Conclusion: Compared to C-Ab, the newly-developed Tn-ED Ab for MUC 1 showed a higher specificity for invasive breast cancer with a low reactivity to non-neoplastic components. Future study plans are ongoing to show that this cancer-specific Tn-ED MUC1 Ab could be useful for differentiating malignant from benign intraductal breast lesions as well. Citation Format: Ai Shimizu, Kanako Hatanaka, Yutaka Hatanaka, Kentaro Naruchi, Masaharu Sato, Hiroshi Kase, Tomoko Mitsuhashi, Hiroko Yamashita, Yoshihiro Matsuno. Cancer-associated MUC1 epitope-recognizing antibody as a novel immunohistochemical marker for breast carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4616.

Mean Computed Tomography Value to Predict the Tumor Invasiveness in Clinical Stage IA Lung Cancer

The purpose of this study was to validate the ability of the mean computed tomography (m-CT) value to predict tumor invasiveness and recurrence, and further, to compare with other measurements such as consolidation/tumor ratio and solid tumor size. A retrospective study was conducted of 494 patients with clinical stage IA lung cancer who had peripherally located lung adenocarcinoma. Receiver operating characteristic curve analysis was used to compare the ability to predict tumor invasiveness and recurrence between m-CT value, consolidation/tumor ratio, and tumor size. Multiple logistic regression analyses were performed to determine the independent variables for the prediction of pathologic, less invasive lung cancer. Disease-free survival was measured from the date of the operation until any recurrence. The m-CT values were 643.6 ± 9.4 Hounsfield units in the noninvasive cancer group and 365.9 ± 11.4 Hounsfield units in the invasive cancer group (p < 0.0001). The invasive cancer group was strongly associated with a high CT attenuation value, high consolidation/tumor ratio, large solid tumor size, large tumor size, and high standardized uptake value. Multiple logistic analyses, including the preoperatively determined variables, revealed that standardized uptake value and m-CT are independent predictive factors of less invasive lung cancer. In addition, the hazard ratio of the m-CT value was higher than that of the standardized uptake value value. The evaluation of m-CT value is useful in predicting less invasive lung cancer. The m-CT value can potentially determine operative procedure, particularly limited resection for peripheral lung adenocarcinoma.

Expression and clinical significance of high risk human papillomavirus and invasive gene in cervical carcinoma.

To study the expression of E6 and E7 mRNA in high-risk human papillomavirus (HPV) HPV-18 and the relationship between the expression of invasive gene and cervical carcinoma. A total of 119 patients with cervical cancer, cervical erosion and cervical HPV infection who were diagnosed in our hospital were selected and randomly divided into two groups: cervical cancer group (n=58) and non-cancerous group (n=61). Another 60 patients with uterine leiomyoma were selected as normal control group. Detection of HPV18 E6, E7 mRNA expression and invasion, migration, proliferation inhibition genes, epithelial mesenchymal transition genes and proliferation related protein content. The relative expression of E6 and E7 HPV-18 in cervical cancer group was significant higher than that in non-cancerous group and control group (mRNA) (P<0.05). The content of TRAF6 and c-FLIP in invasive cervical cancer group was significantly higher than that in non-cancerous group and control group (P<0.05). The mRNA content of CD44v6 and MMP-9 in cervical cancer group was significantly higher than that in non-cancerous group and control group (P<0.05). The content of DEC-1, IKK16, MBP-1 in cervical cancer group was significant lower than that in non-cancerous group and control group (P<0.05). The mRNA content of beta -catenin and Vimentin in cervical cancer group was significantly lower than that in non cancerous group and control group (P<0.05). The proliferation related protein E2F1 of cervical cancer group was significantly lower than that of non-cancerous group and control group, Bmi-1 content was significantly higher than non-cancerous group and control group (P<0.05). The expression of the detection of cervical cancer in high-risk human papilloma virus HPV-18 E6 and E7 mRNA, and the invasion, migration, proliferation inhibition gene, epithelial mesenchymal transition and proliferation related gene protein content, HPV expression rate of mRNA increased with the development of cervical cancer, the expression is also enhanced. The expression has a certain correlation between the level and development of cervical cancer. Through the above indicators, the development of cervical cancer monitoring and treatment to provide important clinical guidance.

Overdiagnosis of thyroid cancer in the Marne and Ardennes Departments of France from 1975 to 2014

ObjectivesIncidence of thyroid cancer has increased considerably in France in recent years, but the mortality rate has declined only slightly. Part of this increased incidence could be attributable to overdiagnosis. We aimed to estimate the contribution of overdiagnosis to the incidence of papillary thyroid cancer. Material and methodsIncidence rates were calculated based on data from the specialised Marnes-Ardennes thyroid cancer registry, for cancers diagnosed between 1975 and 2014, by age category and by five-year period. The population was divided into two groups according to pTNM classification at diagnosis (i.e. localised or invasive). Overdiagnosis was defined as the difference in incidence rates between the invasive cancer and localised cancer groups. This rate was then divided by the incidence rate in the localised cancer group for the most recent period (2010–2014) to obtain the proportion of cancers attributable to overdiagnosis. ResultsIn total, 2008 patients were included. The proportion of incidence attributable to overdiagnosis for the period 2010–2014 was estimated at 7 and 62% in men and women aged < 50 years respectively, and at 65 and 73% respectively in men and women aged ≥ 50 years. ConclusionWe observed a high proportion of cancers attributable to overdiagnosis. This finding raises the issue of patient management, with the risk of overtreatment, and the repercussions on quality of life for patients diagnosed with cancer.

Over diagnosis of thyroid cancer in the Marne and Ardennes departments of France from 1975 to 2014

Incidence of thyroid cancer has increased considerably in France in recent years, but the mortality rate has declined only slightly. Part of this increased incidence could be attributable to over diagnosis. We aimed to estimate the contribution of over diagnosis to the incidence of papillary thyroid cancer. Incidence rates were calculated based on data from the specialised Marnes-Ardennes thyroid cancer registry, for cancers diagnosed between 1975 and 2014, by age category and by five-year period. The population was divided into two groups according to pTNM classification at diagnosis (i.e. localised or invasive). Over diagnosis was defined as the difference in incidence rates between the invasive cancer and localised cancer groups. This rate was then divided by the incidence rate in the localised cancer group for the most recent period (2010–2014) to obtain the proportion of cancers attributable to over diagnosis. In total, 2008 patients were included. The proportion of incidence attributable to over diagnosis for the period 2010–2014 was estimated at 7% and 62% in men and women aged < 50 years respectively, and at 65% and 73% respectively in men and women aged ≥ 50 years. We observed a high proportion of cancers attributable to over diagnosis. This finding raises the issue of patient management, with the risk of over treatment, and the repercussions on quality of life for patients diagnosed with cancer.