Search

Fine needle aspiration cytology (FNAC) is a useful tool in the evaluation of lymphadenopathy. It is a safe and minimally invasive procedure that provides preoperative details for subsequent treatment. It can also diagnose the majority of malignant tumors. However, there are some instances where the diagnosis of tumors remains obscure. To address this, we re-analyzed the misinterpreted patients’ samples using mRNA sequencing technology and then identified the characteristics of non-Hodgkin’s lymphoma that tend to be under-diagnosed. To decipher the involved genes and pathways, we used bioinformatic and biological analysis approaches, identifying the response to oxygen species, inositol phosphate metabolic processes, and peroxisome and PPAR pathways as possibly being involved with this type of tumor. Notably, these analyses identified FOS, ENDOG, and PRKAR2B as hub genes. cBioPortal, a multidimensional cancer genomics database, also confirmed that these genes were associated with lymphoma patients. These results thus point to candidate genes that could be used as biomarkers to minimize the false-negative rate of FNAC diagnosis. We are currently pursuing the development of a gene chip to improve the diagnosis of lymphadenopathy patients with the ultimate goal of improving their prognosis.

Background: Fine needle aspiration cytology (FNAC) is a valuable tool for evaluating lymphadenopathy. The purpose of this study was to assess the reliability and effectiveness of FNAC in the diagnosis of lymphadenopathy. Methods: Cytological characteristics were evaluated in 432 patients who underwent lymph node FNAC and follow-up biopsy at the Korea Cancer Center Hospital from January 2015 to December 2019. Results: Fifteen (3.5%) of the four hundred and thirty-two patients were diagnosed as inadequate by FNAC, with five (33.3%) of these diagnosed as metastatic carcinoma on histological examination. Of the 432 patients, 155 (35.9%) were diagnosed as benign by FNAC, with seven (4.5%) of these diagnosed histologically as metastatic carcinoma. A review of the FNAC slides, however, showed no evidence of cancer cells, suggesting that the negative results may have been due to FNAC sampling errors. An additional five samples regarded as benign on FNAC were diagnosed as non-Hodgkin lymphoma (NHL) by histological examination. Of the 432 patients, 223 (51.6%) were cytologically diagnosed as malignant, with 20 (9.0%) of these diagnosed as tissue insufficient for diagnosis (TIFD) or benign on histological examination. A review of the FNAC slides of these 20 patients, however, showed that 17 (85.0%) were positive for malignant cells. The sensitivity, specificity, positive predictive value (PPV), negative predictive values (NPV), and accuracy of FNAC were 97.8%, 97.5%, 98.7%, 96.0%, and 97.7%, respectively. Conclusions: Preoperative FNAC was safe, practical, and effective in the early diagnosis of lymphadenopathy. This method, however, had limitations in some diagnoses, suggesting that additional attempts may be required according to the clinical situation.

Background Epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancers have emerged as key predictive biomarkers in EGFR tyrosine kinase inhibitor (TKI) treatment. However, a few patients with wild-type EGFR also respond to EGFR TKIs. This study investigated the factors predicting successful EGFR TKI treatment in lung adenocarcinoma patients with wild-type EGFR. Methods We examined 66 patients diagnosed with lung adenocarcinoma carrying wide-type EGFR who were treated with EGFR TKIs. The EGFR gene copy number was assessed by silver in situ hybridization (SISH). We evaluated the clinical factors and EGFR gene copy numbers that are associated with a favorable clinical response to EGFR TKIs. Results The objective response rate was 12.1%, while the disease control rate was 40.9%. EGFR SISH analysis was feasible in 23 cases. Twelve patients tested EGFR SISH-positive, and 11 were EGFR SISH-negative, with no significant difference in tumor response and survival between EGFR SISH-positive and -negative patients. The overall median progression-free survival (PFS) and overall survival (OS) of 66 patients were 2.1 months and 9.7 months, respectively. Female sex and Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0–1 were independent predictors of PFS. ECOG PS 0–1 and a low tumor burden of extrathoracic metastasis were independent predictors of good OS. Conclusion Factors such as good PS, female sex, and low tumor burden may predict favorable outcomes following EGFR TKI therapy in patients with EGFR wild-type lung adenocarcinoma. However, EGFR gene copy number was not predictive of survival.

Introduction: Micro-computed tomography with nanoparticle contrast agents may be a suitable tool for monitoring the time course of the development and progression of tumors. Here, we suggest a practical and convenient experimental method for generating and longitudinally imaging murine liver cancer models. Methods: Liver cancer was induced in 6 experimental mice by injecting clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeats-associated protein 9 plasmids causing mutations in genes expressed by hepatocytes. Nanoparticle agents are captured by Kupffer cells and detected by micro-computed tomography, thereby enabling longitudinal imaging. A total of 9 mice were used for the experiment. Six mice were injected with both plasmids and contrast, 2 injected with contrast alone, and one not injected with either agent. Micro-computed tomography images were acquired every 2- up to 14-weeks after cancer induction. Results: Liver cancer was first detected by micro-computed tomography at 8 weeks. The mean value of hepatic parenchymal attenuation remained almost unchanged over time, although the standard deviation of attenuation, reflecting heterogeneous contrast enhancement of the hepatic parenchyma, increased slowly over time in all mice. Histopathologically, heterogeneous distribution and aggregation of Kupffer cells was more prominent in the experimental group than in the control group. Heterogeneous enhancement of hepatic parenchyma, which could cause image quality deterioration and image misinterpretation, was observed and could be due to variation in Kupffer cells distribution. Conclusion: Micro-computed tomography with nanoparticle contrast is useful in evaluating the induction and characteristics of liver cancer, determining appropriate size of liver cancer for testing, and confirming therapeutic response.

Background It is difficult to correctly diagnose follicular neoplasms (FNs) on fine-needle aspiration cytology (FNAC) because it shares many cytological features with other mimicking lesions. The aim of this study was to identify the cytological features that differentiate FNs from mimicking lesions. Methods We included the cytological slides from 116 cases of thyroid FN diagnosed on FNAC, and included their subsequent histological diagnoses. We evaluated the cytological architectural pattern and nuclear features of the lesions according to their histological groups. Results The final histological diagnoses of the 116 cases varied, and included 51 FNs (44%), 47 papillary thyroid carcinomas (40%) including follicular variant, and seventeen cellular nodular hyperplasias (15%). Regardless of the final histological diagnosis, microfollicular pattern was observed in most cases. On the other hand, trabecular pattern was identified in 34% of FNs, but not in any other lesions. Additionally, elongated nuclei and ground glass chromatin were found in only some papillary thyroid carcinomas. Conclusions This study shows that the trabecular pattern is a representative cytological feature of FNs that can be used to distinguish FNs from mimicking lesions. In addition, nuclear shape and chromatin pattern can be used to further confirm the diagnosis of FNs from mimicking lesions through FNAC.

Background Although histological diagnosis of pilomatricoma is not difficult because of its unique histological features, cytological diagnosis through fine-needle aspiration cytology (FNAC) is often problematic due to misdiagnoses as malignancy. Methods We reviewed the cytological features of 14 cases of histologically-proven pilomatricoma from Korea Cancer Center Hospital, with a discussion on the diagnostic pitfalls of FNAC. Results Among 14 cases of pilomatricoma, 10 (71.4%) were correctly diagnosed through FNAC, and two (14.3%) were misdiagnosed as carcinoma. Cytologically, all cases had easily recognizable clusters of basaloid cells and foreign body-type multinucleated cells. Although ghost cells were also found in all cases, some were inconspicuous and hardly recognizable due to their small numbers. Conclusions An accurate diagnosis of pilomatricoma in FNAC is feasible with consideration of clinical information and close examination of ghost cells.

Background Trophoblast antigen 2 (TROP2) is a human trophoblast cell-surface glycoprotein that is overexpressed in several types of epithelial cancers, and is suggested to be associated with an unfavorable prognosis. BRAF mutations are the most common genetic alteration in papillary thyroid carcinoma (PTC). We evaluated the correlation between TROP2 expression and BRAF mutation in PTC. Methods First, we carried out pyrosequencing for BRAF mutations and immunohistochemistry for TROP2 expression with a tissue microarray consisting of 52 PTC cases. Membranous staining in at least 5% of tumor cells was designated as positive staining and we analyzed the relationship between TROP2 expression and diverse clinicopathological factors, including BRAF mutation. Second, we tested TROP2 mRNA expression in three thyroid cancer cell lines with BRAF mutations (BCPAP, SNU790, and 8505C) and a normal thyroid cell line. Additionally, we checked TROP2 protein levels in a normal thyroid cell line after introduction of the BRAF V600E mutation. Results In this study, 21 of 26 cases with BRAF mutation showed TROP2 immunoreactivity, whereas all 26 cases without BRAF mutation showed no immunoreactivity for TROP2 with a statistically significant difference (p

Tumor implantation of lung cancer at the wire localization site has not been reported previously while there have been several reported cases of chest wall implantation after percutaneous core needle biopsy and chest tube insertion for malignant pleural effusion. We report the case of a 64-year-old-man with lung cancer (squamous cell carcinoma). The patient had lung cancer implantation in the chest wall 8 months after computed tomography-guided wire localization and subsequent anterior segmentectomy of right upper lobe with mediastinal lymph node dissection.

BACKGROUND: The aim of this study was to investigate the association between epidermal growth factor receptor (EGFR) mutation and thyroid cancer in female patients with nonsmall-cell lung cancer (NSCLC). METHODS: In a retrospective study, we examined 835 female patients who were diagnosed with NSCLC and underwent an EGFR mutation test between June 2003 and August 2013. The associations of EGFR mutation with thyroid cancer and a family history of thyroid cancer were evaluated using logistic regression models. RESULTS: EGFR mutation was found in 378 of 835 patients. In addition to adenocarcinoma (P < 0.001), EGFR mutations were positively associated with a personal history of thyroid cancer (5.8% versus 2.6%; P = 0.020), while showing a trend toward inverse association with a personal history of nonthyroid cancer (5.8% vs. 9.0%; P = 0.086). Likewise, the incidence of EGFR mutations was associated with a family history of thyroid cancer (2.9% vs. 0.9%; P = 0.028), while showing a trend toward inverse association with a family history of nonthyroid cancer (27.8% vs. 33.7%; P = 0.066). Multivariate logistic regression showed that the incidence of EGFR mutations was different in women with thyroid or nonthyroid cancer (P = 0.035) and in women with a family history of thyroid or nonthyroid cancer (P = 0.023). CONCLUSIONS: Our data suggest that thyroid cancer and a family history of thyroid cancer are associated with EGFR-mutated NSCLC in female patients. The differences in the incidence of thyroid cancer and a family history of thyroid cancer by EGFR mutational status provide new insight into pathogenesis of this genetic change.

Background: It is difficult to distinguish parathyroid lesions (PLs) from thyroid lesions using fine needle aspiration cytology (FNAC) because of their proximity and their similar cytomorphological features. Methods: FNAC smears of 46 patients with pathologically proven PLs that were histologically diagnosed as parathyroid adenoma (PA, n = 35), parathyroid hyperplasia (PH, n = 3), atypical parathyroid adenoma (APA, n = 1), and parathyroid carcinoma (PC, n = 7) were retrospectively reviewed and analyzed. Results: Our initial cytological diagnoses indicated correct diagnoses in 31 of 46 PL patients (67%). The 15 erroneous diagnoses were 5 patients with non-specific benign disease (11%), 4 with nodular hyperplasia of the thyroid (9%), 5 with atypical cells (11%), and 1 with a metastatic papillary thyroid carcinoma (2%). Follicular pattern, papillary structures, colloid-like material, and macrophages, which often suggest thyroid lesions, were also present in some PLs. We found that branching capillaries along the papillary structures, stippled nuclear chromatin, and frequent occurrence of naked nuclei were useful for determining a parathyroid origin. Conclusions: It is important to be aware that PLs are frequently mistaken for thyroid lesions based on FNAC. The specific and unique characteristics of PLs identified here may be helpful in diagnosis.

Purpose The Notch signaling pathway is widely expressed in normal, reactive, and neoplastic tissues; however, its role in thyroid tissues has not been fully elucidated. Therefore, this study was conducted to characterize the expression of the Notch signaling pathway in papillary thyroid cancer (PTC) cells and anaplastic thyroid cancer (ATC) cells. Materials and Methods Expression of activated Notch1 in ATC and PTC paraffin-embedded tissues was determined by immunohistochemistry. The small interfering RNA technique was employed to knock down Notch1 expression in ATC and PTC cell lines. Results The expression of activated Notch1 was higher in ATC cases than in PTC cases. Inhibition of Notch1 significantly reduced proliferation and migration of ATC cells, but not PTC cells. In addition, inhibition of Notch1 in ATC cells significantly reduced the expression of key markers of epithelial-mesenchymal transition and cancer stem cells. Conversely, changes in the expression of these proteins were not observed in PTC cells. Conclusion The results of this study suggest that Notch1 expression plays different roles in tumor progression in ATC and PTC cells. We also found that Notch1 expression was significantly related to the highly invasive or proliferative activity of ATC cells. [ABSTRACT FROM AUTHOR]

Objective: This study explored the potential association between epidermal growth.factor receptor. (EGFR) mutation status and brain metastasis in patients with nonadenocarcinoma nonsmall cell lung cancer. (NSCLC).Patients and Methods: We analyzed clinical data from 286 patients with nonadenocarcinoma NSCLC, who were tested for EGFR mutations and underwent brain magnetic resonance imaging at diagnosis. We examined the relationship between EGFR mutation and brain metastasis at initial presentation.Results: Of the 286 patients, 20 patients (7.0%) had EGFR mutations. EGFR mutations were more frequent in younger patients (11.1% in patients =64 years vs. 3.3% in patients >64 years: P = 0.01), females (21.4% vs. 3.5% in males: P <0.001), never-smokers (25.0% vs. 3.4% in smokers: P < 0.001), and tumors with nonsquamous histology (25.0% vs. 4.1% in squamous histology: P < 0.001). At diagnosis, the frequency of EGFR mutations was significantly different in patients with metastasis to different sites (4.0% [no metastases] vs. 10.4% [extracranial metastases] vs. 40.0% [brain metastases], P < 0.001). The strong association between EGFR mutation and brain metastasis remained significant in multivariate analysis (adjusted odds ratio [OR] = 9.68, 95% confidence interval [CI] =2.32-40.45; P = 0.002). Associations were also found for EGFR mutation status with nonsquamous histology (adjusted OR = 4.46, 95% CI = 1.46-13.56; P = 0.008).Conclusion: This study indicates that the likelihood of nonadenocarcinoma patients having EGFR mutant tumors may differ according to brain metastasis and squamous cell histology. [ABSTRACT FROM AUTHOR]

There have been several epidemiological studies of the association between 25-hydroxyvitamin D (25(OH)D) level and lung cancer risk. We explored the potential association between serum 25(OH)D levels and mutations in epidermal growth factor receptor (EGFR) in patients with pulmonary adenocarcinoma. We analyzed clinical data from 135 patients whose serum 25(OH)D levels were measured and EGFR mutational status was tested at the time of diagnosis. The relationship between 25(OH)D and clinical factors such as EGFR mutational status and sex was examined. The median serum 25(OH)D level in patients with pulmonary adenocarcinoma was 16.8 ng/ml (range: 3.0-84.3 ng/ml). The level of 25(OH)D was lower in female patients than in male patients (P=0.03). Interestingly, 25(OH)D levels of patients with EGFR-mutated tumors were low compared with those with wild-type tumors (median 18.2 vs 14.7 ng/ml, P=0.011). After a dose-response relationship between EGFR mutations and 25(OH)D levels (as a continuous variable) was observed (OR = 0.96, P = 0.036), we categorized 25(OH)D levels as low (<16.8 ng/ml) and high ( >16.8 ng/ml). Multivariate analysis revealed the association between low 25(OH)D levels and a high incidence of EGFR mutations (adjusted OR = 2.42, 95% CI: 1.11-5.26, P=0.026). The results from this study indicate that low 25(OH)D levels are associated with EGFR mutations in pulmonary adenocarcinoma. [ABSTRACT FROM AUTHOR]

Background: There has been an increase in the use of fine needle aspiration cytology (FNAC) for the diagnosis of parathyroid lesions (PLs). Differentiation between a thyroid lesion and a PL is not easy because of their similar features. We reviewed parathyroid aspirates in our institution and aimed to uncover trends in diagnostic criteria. Methods: We selected 25 parathyroid aspirates (from 6 men and 19 women) confirmed surgically or immunohistochemically from 2006 to 2011. Results: Major architectural findings of PLs include scattered naked nuclei, loose clusters, a papillary pattern with a fibrovascular core, tight clusters, and a follicular pattern. These architectures were commonly admixed with one another. Cytological features included anisokaryosis, stippled chromatin, a well-defined cell border, and oxyphilic cytoplasm. Eighteen of the 25 patients were diagnosed with PL using FNAC. Seven patients had been misdiagnosed with atypical cells (n=2), benign follicular cells (n=2), adenomatous goiter (n=2) and metastatic carcinoma (n=1) in FNAC. Using clinicoradiologic data, the sensitivity of the cytological diagnosis was 86.7%. The cytological sensitivity decreased to 50% without this information. Conclusions: FNAC of PL is easily confused with thyroid lesions. A combination of cytological parameters and clinical data will be required to improve the diagnostic sensitivity of PLs. [ABSTRACT FROM AUTHOR]

Purpose: We performed a pilot study to determine the benefit of high-dose chemotherapy and autologous peripheral blood stem cell transplantation (HDCT/autoPBSCT) for patients with Ewing sarcoma family of tumors. Methods: We retrospectively analyzed the data of patients who received HDCT/autoPBSCT at Korea Cancer Center Hospital. Patients with relapsed, metastatic, or centrally located tumors were eligible for the study. Results: A total of 9 patients (3 male, 6 female), with a median age at HDCT/autoPBSCT of 13.4 years (range, 7.1 to 28.2 years), were included in this study. Patients underwent conventional chemotherapy and local control either by surgery or radiation therapy, and had achieved complete response (CR, n=7), partial response (n=1), or stable disease (n=1) prior to HDCT/autoPBSCT. There was no transplant-related mortality. However, the median duration of overall survival and event-free survival after HDCT/autoPBSCT were 13.3 months (range, 5.3 to 44.5 months) and 6.2 months (range, 2.1 to 44.5 months), respectively. At present, 4 patients are alive and 5 patients who experienced adverse events (2 metastasis, 2 local recur, and 1 progressive disease) survived for a median time of 2.8 months (range, 0.1 to 10.7 months). The 2-year survival after HDCT/autoPBSCT was 44.4%±16.6% and disease status at the time of HDCT/autoPBSCT tended to influence survival (57.1%±18.7% of cases with CR vs. 0% of cases with non-CR, P =0.07). Conclusion: Disease status at HDCT/autoPBSCT tended to influence survival. Further studies are necessary to define the role of HDCT/autoPBSCT and to identify subgroup of patients who might benefit from this investigational treatment [ABSTRACT FROM AUTHOR]

Purpose Features of epidermal growth factor receptor (EGFR) expression in osteosarcoma and in vitro efficacies of EGFR inhibitors against osteosarcoma cells were evaluated. Materials and Methods Thirty biopsy samples of osteosarcoma patients were retrospectively analyzed for EGFR protein expression by immunohistochemistry. Relationships between EGFR expression and clinicopathologic characteristics and treatment outcomes were evaluated. Four osteosarcoma cell lines were analyzed for EGFR and p-EGFR expression by western blotting. Efficacies of gefitinib and BIBW2992 on osteosarcoma cells were evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Tyrosine kinase domains in exons 18 to 21 were sequenced and gene expression analyses of EGFR and PTEN were performed in four osteosarcoma cell lines. Results EGFR protein was expressed in 27 (90%) samples (6 low, 12 intermediate, 9 high) and in three cell lines. Intermediate or high staining for EGFR was related to a tumor volume < 150 mL (p < 0.001) and histologic subtype other than osteoblastic type (p=0.03). However, EGFR expression was not associated with histologic response to preoperative chemotherapy or survival. Gefitinib and BIBW 2992 did not have any significant inhibitory effect on cell viabilities. DNA sequencing analysis revealed three osteosarcoma cell lines have single base changes at codon 2361 of exon 20 (G to A), without affecting translation results. Furthermore, no mutation was found to be associated with constitutive EGFR activation. Conclusion In the present study, gefitinib and BIBW2992 were not effective against osteosarcoma cells. However, as osteosarcoma cells express EGFR, further studies are necessary to explore the potential of other therapeutic agents targeting EGFR. [ABSTRACT FROM AUTHOR]

Purpose: We did this retrospective study to explore the association between epidermal growth factor receptor (EGFR) mutation and clinical features in postoperative recurrent female non-small-cell lung cancer (NSCLC). Materials and Methods: We reviewed clinical data on 86 female patients who had postoperative recurrent disease between December 1992 and July 2007. The start of tyrosine kinase inhibitor therapy was treated as a censoring event. Corresponding surgical specimens of primary tumors were used to test for EGFR mutations. Results: Thirty patients presented with local recurrence and distant recurrence was identified in 56. Thirty-four of the 86 patients (40%) harbored EGFR mutations. Patients with distant recurrence were more likely to have EGFR mutations than patients with local recurrence (48% versus 23%; P = 0.024). On multivariate analysis, distant recurrence was associated with a high frequency of EGFR mutations (OR, 3.3; P = 0.028). Survival analysis showed poor survival of patients with mutated EGFR (HR, 2.3; P = 0.017) or with non-adenocarcinoma histology (HR, 3.3; P = 0.001). Conclusion: The association between recurrence pattern and EGFR mutation status was suggested in recurrent female NSCLC patients. In addition, our data indicate unfavorable disease process of EGFR mutated tumors. Further studies need to be conducted to validate these findings. [ABSTRACT FROM AUTHOR]

Synovial sarcoma arises in the para-articular tissues, and it can also occur in various unexpected sites. We report a rare case of primary monophasic synovial sarcoma (MSS) arising in the mesentery. A 59-year-old man presented with a palpable abdominal mass. On microscopic examination, the entire tumor comprised a dense proliferation of the spindle cells without epithelial components. The tumor cells were positive for transducin-like enhancer of split 1, bcl-2, epithelial membrane antigen and CD99 but negative for CD34, CD117, alpha-smooth muscle actin, cytokeratin, and calretinin on immunohistochemistry. The reverse transcriptase-polymerase chain reaction revealed a single 151-bp fragment representing the SYT-SSX2 fusion transcript. Because mesenteric MSS is extremely rare and many cases display histologic findings that overlap with those of more frequently involved tumors such as hemangiopericytoma and gastrointestinal stromal tumor, there is a chance of making an incorrect diagnosis that can result in an inappropriate treatment. [ABSTRACT FROM AUTHOR]

We performed this retrospective study to assess the association of epidermal growth factor receptor (EGFR) with metastatic presentations in advanced non-small cell lung cancer (NSCLC). The data from 125 patients with stage III or IV NSCLC were analyzed. We detected EGFR mutations in 36 NSCLC patients. EGFR mutations were predominant in never-smokers (P < .001), patients with adenocarcinomas (P < .001), and female patients (P < .001). When the metastatic sites were analyzed, pleural metastases were associated with a high incidence of EGFR mutations (P = .028). Particularly, pleural metastases with minimal effusion (PMME) were associated with EGFR mutational status (P = .001). Patients with N3 lesions were less likely to harbor EGFR mutations (P = .033). On multivariate analysis, N3 lesions (P = .017) and PMME (P < .001) remained significant factors for EGFR mutations. EGFR mutations may be associated with different presentations of pleural and N3 nodal metastases. [ABSTRACT FROM AUTHOR]

In this retrospective study, we evaluated to what extent diagnostic delays impact prognosis in osteosarcoma. The authors identified 26 osteosarcoma patients who had undergone inappropriate procedure-associated diagnostic delays of more than 45 days after surgery, calculated overall survival rates, and analyzed clinicopathologic characteristics. Initial clinical impressions were of a benign bone tumor in 15 patients, fracture in 8, and infection in 3. After initial inappropriate procedures, primary surgeons failed to send a tissue sample to a pathologist for definite diagnosis in 12 cases, and pathologists made incorrect diagnoses in the other 14. The average doctor-associated diagnostic delay after inappropriate surgery for these 26 patients was 10.5 months. Following referral to our institute, 22 underwent both surgery and chemotherapy and the remaining 4 patients underwent chemotherapy only. Four of the 26 patients were alive at last follow-ups. Estimated 5- and 10-year overall survival rates were 26 and 10%, respectively. The present study shows that doctor-associated diagnostic delay superimposed on an inappropriate primary procedure has a significant detrimental effect on overall survival in osteosarcoma. This study demonstrates that surgeons and pathologists should spare no effort to minimize diagnostic errors and delays. [ABSTRACT FROM AUTHOR]

In this retrospective study, we assessed tumor growth patterns as visualized on MR images, and examined whether tumor growth patterns correlate with clinicopathologic variables. In addition, we also evaluated the relationship between patient outcome and tumor growth pattern in the whole study cohort and in subsets of AJCC IIA and IIB patients. We retrospectively reviewed 347 patients with Enneking stage IIB and AJCC stage II osteosarcoma that was treated with surgery and neoadjuvant chemotherapy at our institute. Patients were divided into three groups based on tumor growth pattern, namely, concentric, eccentric, and longitudinal groups. Fisher’s exact test was performed to analyze correlations between tumor growth patterns and clinicopathological variables. Five-year metastasis-free survival and overall survival were evaluated using univariate and multivariate analyses. In terms of tumor growth patterns, 225 patients (64.8%) had a concentric, 71 (20.5%) an eccentric and 51 (14.7%) a longitudinal tumor. Eccentric tumors were usually small and responded well to chemotherapy, whereas concentric tumors were large and responded poorly. The prognostic significances of tumor growth patterns were confirmed by univariate and multivariate analyses. Among AJCC stage IIA patients, no survival difference was found according to growth pattern, whereas in AJCC stage IIB patients, longitudinal tumors were associated with significantly better survival than concentric tumors. Tumor growth pattern was found to be an independent prognostic factor in stage II osteosarcoma. Moreover, longitudinally growing tumors were associated with better survival in AJCC stage IIB patients. Our results suggest that tumor growth pattern could be used as an indicator of risk-adapted therapy when combined with other prognostic factors. [ABSTRACT FROM AUTHOR]

Abstract Objective  In this retrospective study, we assessed the plain-film radiographic patterns of American Joint Committee on Cancer (AJCC) stage II osteosarcoma and analyzed the relationship between these patterns and clinicopathologic variables. Materials and methods  We retrospectively reviewed 347 patients with AJCC stage II osteosarcoma who were treated at our institute. Patients were divided into three groups based on radiographic patterns, i.e., osteoblastic, osteolytic, and mixed. Fisher’s exact chi-square test was performed to analyze correlations between radiographic patterns and clinicopathological variables. Results  One hundred and eighty-eight patients had an osteoblastic tumor, 101 had an osteolytic tumor, and 58 had a mixed tumor. Tumors with an osteoblastic pattern showed a tendency to have the following characteristics: AJCC stage II-B, osteoblastic or chondroblastic subtype, and no pathologic fracture. Conversely, osteolytic tumors were frequently of AJCC stage II-A, had a fibroblastic or rare subtype, and were associated with a pathologic fracture. Finally, mixed tumors were frequently found in men. No survival difference was found according to radiographic pattern. Conclusions  Plain-film radiographic patterns were found to be related with clinicopathological features. We believe that it could be used to provide valuable information for treatment decision-making in cases of high-grade extremity osteosarcoma. [ABSTRACT FROM AUTHOR]

Abstract Background To propose a personalized therapeutic approach in osteosarcoma treatment, we assessed whether sequential [18F]FDG PET/CT (PET/CT) could predict the outcome of patients with osteosarcoma of the extremities after one cycle and two cycles of neoadjuvant chemotherapy. Methods A total of 73 patients with AJCC stage II extremity osteosarcoma treated with 2 cycles of neoadjuvant chemotherapy, surgery, and adjuvant chemotherapy were retrospectively analyzed in this study. All patients underwent PET/CT before (PET0), after 1 cycle (PET1), and after the completion of neoadjuvant chemotherapy (PET2), respectively. Maximum standardized uptake value (SUVmax) (corrected for body weight) and the % changes of SUVmax were calculated, and histological responses were evaluated after surgery. Receiver-operating characteristic (ROC) curve analyses and the Cox proportional hazards models were used to analyze whether imaging and clinicopathologic parameters could predict event-free survival (EFS). Results A total of 36 patients (49.3%) exhibited a poor histologic response and 17 patients (23.3%) showed events (metastasis in 15 and local recurrence in 2). SUVmax on PET2 (SUV2), the percentage change of SUVmax between PET0 and PET1 (Δ%SUV01), and between PET0 and PET2 (Δ%SUV02) most accurately predicted events using the ROC curve analysis. SUV2 (relative risk, 8.86; 95% CI, 2.25–34.93), Δ%SUV01 (relative risk, 5.97; 95% CI, 1.47–24.25), and Δ%SUV02 (relative risk, 6.00; 95% CI, 1.16–30.91) were independent predicting factors for EFS with multivariate analysis. Patients with SUV2 over 5.9 or Δ%SUV01 over − 39.8% or Δ%SUV02 over − 54.1% showed worse EFS rates than others (p < 0.05). Conclusions PET evaluation after 1 cycle of presurgical chemotherapy can predict the clinical outcome of extremity osteosarcoma. [18F]FDG PET, which shows a potential role in the early evaluation of the modification of timing of local control, can be a useful modality for early response monitoring of neoadjuvant chemotherapy.

BACKGROUND: The level of proliferation activity is a strong prognostic or predictive indicator in breast cancer, but its optimal measurement is still in debate, necessitating new proliferation markers. In the present study, the prognostic significance of the CKAP2-positive cell count (CPCC), a new proliferation marker, was evaluated, and the results were compared with those for the mitotic activity index (MAI). METHODS: This study included 375 early-stage breast cancer samples collected from two institutions between 2000 and 2006. Immunohistochemical staining was performed using a CKAP2 monoclonal antibody. Cox proportional hazard regression models were fitted to determine the association between the CPCC and relapse-free survival (RFS) amongst three groups formed on the basis of the CPCC or MAI value: groups 2 and 3 showing the middle and highest values, respectively, and group 1 the lowest. RESULTS: After adjustment for age, T stage, N stage, HER2 status, estrogen receptor status, progesterone receptor status, institution, and year of surgical resection, the CPCC was associated with a significantly worse RFS {hazard ratio [HR] = 4.10 (95% CI: 1.64-10.29) for group 2; HR = 4.35 (95% CI: 2.04-10.35) for group 3}. Moreover, its prognostic significance was similar to or higher than that based on the MAI {HR = 2.05 (95% CI: 0.94-4.65) for group 2; HR = 2.35 (95% CI: 1.09-5.10) for group 3}. In subgroup analyses, the CPCC showed a prognostic significance in the luminal A and triple-negative subgroups, but not in the HER2-positive subgroup. CONCLUSIONS: Chromatin CKAP2 is an independent prognostic marker for RFS in early-stage breast cancer, and could potentially replace the MAI in clinical evaluation of proliferation activity. Additionally, our study results suggest that the prognostic significance of proliferation activity differs among the various subgroups of breast cancer.