Background Cellular senescence is defined as an irreversible cell cycle arrest caused by various internal and external insults. While the metabolic dysfunction of senescent cells in normal tissue is relatively well-established, there is a lack of information regarding the metabolic features of senescent tumor cells.
Methods Publicly available single-cell RNA-sequencing data from the GSE166555 and GSE178341 datasets were utilized to investigate the metabolic features of senescent tumor cells. To validate the single-cell RNA-sequencing data, we performed senescence-associated β-galactosidase (SA-β-Gal) staining to identify senescent tumor cells in fresh frozen colorectal cancer tissue. We also evaluated nicotinamide adenine dinucleotide dehydrogenase–tetrazolium reductase (NADH-TR) and succinate dehydrogenase (SDH) activity using enzyme histochemical methods and compared the staining with SA-β-Gal staining. MTT assay was performed to reveal the complex 1 activity of the respiratory chain in in-vitro senescence model.
Results Single-cell RNA-sequencing data revealed an upregulation in the activity of complexes 1 and 2 in oxidative phosphorylation, despite overall mitochondrial dysfunction in senescent tumor cells. Both SA-β-Gal and enzyme histochemical staining using fresh frozen colorectal cancer tissues indicated a high correlation between SA-β-Gal positivity and NADH-TR/SDH staining positivity. MTT assay showed that senescent colorectal cancer cells exhibit higher absorbance in 600 nm wavelength.
Conclusions Senescent tumor cells exhibit distinct metabolic features, characterized by upregulation of complexes 1 and 2 in the oxidative phosphorylation pathway. NADH-TR and SDH staining represent efficient methods for detecting senescent tumor cells in colorectal cancer.
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Primary cribriform carcinoma of the skin is an indolent, rare, adnexal tumor. Although its malignant potential remains uncertain, no recurrence or metastasis has been reported. A 33-year-old man presented with a solitary, erythematous, subcutaneous nodule on the right knee. The clinical impression was epidermal cyst, and the resected tumor demonstrated a well-circumscribed mass in the dermis and subcutis. The tumor was composed of two regions: a solid component and a cribriform component. The solid component (90%) showed multiple solid nests of epithelial cells. Individual cells had large, oval-to-round, hyperchromatic, pleomorphic nuclei with a nuclear groove. The cribriform component (10%) showed similar neoplastic cells with many prominent lumina. Some lumina had an eosinophilic substance that exhibited a positive periodic acid-Schiff reaction. No recurrence or metastasis was observed within a followup period of eight months after excision. In conclusion, we report the first case of primary cribriform carcinoma of the skin in Korea.
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Background Recent findings in molecular pathology suggest that genetic translocation and/oroverexpression of oncoproteins is important in salivary gland tumorigenesis and diagnosis. Weinvestigated PLAG1, SOX10, and Myb protein expression in various salivary gland neoplasm tissues.
Methods A total of 113 cases of surgically resected salivary gland neoplasms at the NationalCancer Center from January 2007 to March 2017 were identified. Immunohistochemical stainingof PLAG1, SOX10, and Myb in tissue samples was performed using tissue microarrays.
Results Among the 113 cases, 82 (72.6%) were benign and 31 (27.4%) were malignant. PLAG1 showednuclear staining and normal parotid gland was not stained. Among 48 cases of pleomorphicadenoma, 29 (60.4%) were positive for PLAG1. All other benign and malignant salivary glandneoplasms were PLAG1-negative. SOX10 showed nuclear staining. In normal salivary gland tissuesSOX10 was expressed in cells of acinus and intercalated ducts. In benign tumors, SOX10 expressionwas observed in all pleomorphic adenoma (48/48), and basal cell adenoma (3/3), but not inother benign tumors. SOX10 positivity was observed in nine of 31 (29.0%) malignant tumors.Myb showed nuclear staining but was not detected in normal parotid glands. Four of 31 (12.9%)malignant tumors showed Myb positivity: three adenoid cystic carcinomas (AdCC) and onemyoepithelial carcinoma with focal AdCC-like histology.
Conclusions PLAG1 expression is specificto pleomorphic adenoma. SOX10 expression is helpful to rule out excretory duct origin tumor,but its diagnostic value is relatively low. Myb is useful for diagnosing AdCC when histology isunclear in the surgical specimen.
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Background Core needle biopsy is a relatively new technique used to diagnose salivary gland lesions, and its role in comparison with fine needle aspiration cytology needs to be refined. Methods: We compared the results of 228 ultrasound-guided core needle biopsy and 371 fine needle aspiration procedures performed on major salivary gland tumors with their postoperative histological diagnoses. Results: Core needle biopsy resulted in significantly higher sensitivity and more accurate tumor subtyping, especially for malignant tumors, than fine needle aspiration. No patient developed major complications after core needle biopsy. Conclusions: We recommend ultrasoundguided core needle biopsy as the primary diagnostic tool for the preoperative evaluation of patients with salivary gland lesions, especially when malignancy is suspected.
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BACKGROUND Rapid and sensitive detection of KRAS mutation is needed to maximize the benefits for patients who are being treated with monoclonal antibodies to target the epidermal growth factor receptor in colorectal cancer. The aim of this study is to evaluate the efficacy of the peptide nucleic acid clamp real-time PCR (PCqPCR) as compared to that of direct sequencing (DS) between using fresh colorectal cancer tissue and the matched formalin-fixed and paraffin-embedded (FFPE) colorectal cancer tissue. METHODS The efficacy of PCqPCR was evaluated and compared with that of DS using fresh tissue and matched FFPE tissue from 30 cases of colorectal cancer. RESULTS PCqPCR is more sensitive than DS for detecting KRAS mutation. PCqPCR detected 1% of mutants in 1 ng DNA. PCqPCR detected mutation in 1% of mutant cells, while DS barely detected, by manual reading, that in 20-50% of mutant cells.
In the clinical samples, PCqPCR detected KRAS mutation in 60.0% while DS detected KRAS mutation in 53.3% of the colorectal cancers. The two methods showed a 100% concordance rate for detecting KRAS mutation between the fresh tissue and FFPE tissue. CONCLUSIONS The PCqPCR method is efficiently applicable for the detection of KRAS mutation in a clinical setting.
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Jeong Hwan Park, Ho Joong Youn, Jung Sook Yoon, Chul Soo Park, Soo Sung Oh, Woo Baek Chung, Jong Won Chung, Yun Seok Choi, Dong Hyun Lee, Yong Seog Oh, Wook Sung Chung, Soon Jo Hong, Youn Soo Lee, Sung Bo Sim, Sun Hee Lee
BACKGROUND In vitro experimental studies have reported that transforming growth factor-beta1 (TGF-beta1) stimulates the production of alpha-smooth muscle actin (alpha-SMA) in porcine valves. However, the relation between TGF-beta1 and alpha-SMA in myxomatous valves has not been elucidated. METHODS We classified 27 subjects into two groups: 1) myxomatous group (M:F=11:12, mean age=55+/-15 years) and 2) rheumatic group (M:F=3:1, mean age=41+/-17 years) according to preoperative echocardiographic and postoperative histologic findings. Twenty-seven valve specimens from the patients who underwent valve replacement were obtained.
Tissue samples were analyzed by immunohistochemistry for TGF-beta1 and alpha-SMA. The positively stained areas were measured using an image analysis program (Image Pro-Plus 4.5), and then the TGF-beta1 volume fraction (TGF-VF) and alpha-SMA volume fraction (alpha-SMA-VF) were calculated. RESULTS TGF-VF in myxomatous valves was higher than in rheumatic valves (2,759+/-2,294 vs 864+/-276, p=0.04).
alpha-SMA-VF in myxomatous valves was higher than in rheumatic valves (4,122+/-2,275 vs 2,421+/-844, p=0.002).
There was a significant correlation between TGF-beta1 and alpha-SMA in myxomatous valves (r=0.38, p=0.04). There was no significant correlation between TGF-beta1 and alpha-SMA in rheumatic valves (r=-0.50, p=0.67). CONCLUSIONS TGF-beta1 and alpha-SMA may be related to the pathogenesis of myxomatous valves. The activation of TGF-beta1 might increase the expression of alpha-SMA in human myxomatous valves.
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Mutation of the p53 gene is one of the most common genetic alterations in invasive breast carcinoma. However, it is unclear that the mutation usually occurs in noninvasive breast lesions. It might be expected that there is a correlation between histologic progression of breast lesions and proliferative rate. We investigated the expression of p53 protein and Ki-67 labelling index (LI) using immunohistochemistry in 16 ductal carcinoma in situ with microinvasion (DCIS-Mi), 56 DCIS, 15 atypical ductal hyperplasia (ADH), and 7 intraductal hyperplasia (IDH).
Expression of p53 protein was detected in 33.9% of DCIS and 56.3% of DCIS-Mi and was confined exclusively in Van Nuys DCIS group 2 and 3. In ADH and IDH, no expression of p53 protein was found.
There was no significant correlation between Van Nuys DCIS groups and Ki-67 LI. In conclusion, p53 mutation may be involved in the neoplastic progression from ADH to DCIS and is directly related to high nuclear grade and associated necrosis of DCIS.
BACKGROUND Core needle biopsy (CNB) is widely used as the initial sampling method for breast cancer. And because frozen section (FS) diagnosis is rapid and reliable, we studied the diagnostic agreement between the diagnosis of FS of CNB and final diagnosis after surgery to evaluate the diagnostic accuracy of the FS of CNB. METHODS Of 409 patients who were preoperatively diagnosed by FS of CNB and who underwent final surgery from 1996 through 2000, 24 cases were found to be ductal carcinoma in situ (DCIS) and 385 cases invasive carcinoma (IC). The diagnoses of FS of CNB were compared with final diagnoses. RESULTS The diagnostic accuracy of carcinoma is 63.6% for DCIS and 86.9% for invasive carcinoma. Five cases (1.2%) could not be diagnosed because of material insufficiency for diagnosis. Twenty two cases (5.4%) were diagnosed as benign on FS, among which 20 (90.9%) were misdiagnosed by sampling error. Twenty seven cases (6.7%) were deferred on FS, 4 of these cases were DCIS, 5 were invasive lobular carcinoma (ILC), the rest displayed low nuclear grades or marked freezing artifacts. CONCLUSIONS The diagnostic accuracy of FS of CNB is very high except for cases of ILC and low grade DCIS. Considering the advantage of rapid evaluation, more definitive diagnosis, familiarity by pathologists and availability of ancillary study, FS of CNB is very useful method as the preoperative evaluation.
Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare type of kidney tumor that has only been recently described. Furthermore, a case of MTSCC associated with a simultaneous lung cancer in the same patient has never been reported in the literature. In this paper, we describe a kidney tumor that was detected during staging work-up in a 72-year-old lung cancer patient. The kidney tumor was removed and shown to exhibit histological and immunophenotypic features of MTSCC, completely distinct from the pulmonary adenocarcinoma. In addition, this case was unique because it was characterized by neuroendocrine differentiation as well as p53 and Ki-67 overexpression in tumor cells. Therefore, we report a case of MTSCC diagnosed in a patient with pulmonary adenocarcinoma and describe the detailed histologic and immunohistochemical features of MTSCC.
BACKGROUND Juvenile ossifying fibroma (JOF) is defined as a variant of the ossifying fibroma, and the latter includes juvenile trabecular ossifying fibroma (JTOF) and juvenile psammomatoid ossifying fibroma (JPOF). JOF can be distinguished from other craniofacial fibroosseous lesions by its tendency to recur and its clinical mimicry of malignant bone tumors, but some clinical and histological features of JOF overlap with the other fibro-osseous lesions as well. We aimed to identify the clinicopathologic definition of JOF. METHODS Forty-two cases of fibro-osseous lesions were reviewed and they were classified into JOF, fibrous dysplasia (FD) and ossifying fibroma (OF). RESULTS JTOF had long, slender and anastomosing trabeculae of osteoid in a fibrocellular stroma, and JPOF had small ossicles resembling psammoma bodies with a thick collagenous rim in the fibrous stroma, which are features that differ from those of FD and OF. Radiologically, JOF and OF showed a well-defined lesion but FD exhibited an ill-defined lesion.
Clinically, the average age of the JOF patients was the youngest, followed by OF and FD. For JOF, three cases had rapid growth and two others showed recurrences. JOF mainly occurred in the paranasal sinuses, OF in the mandible and FD in any craniofacial bone. CONCLUSION We demonstrated the distinct characteristics of JOF and these features may be helpful for the diagnosis and management of this malady.
Ectopic hamartomatous thymoma (EHT) is a rare and distinctive benign neoplasm of the lower neck. We here report on a case of EHT arising in the suprasternal area of 47-year-old male patient. The well-circumscribed mass measured 7 x 6 x 4 cm and it predominantly had a solid gray-white cut surface. Microscopically, the tumor consisted of spindle cells, epithelial nests, and mature adipose tissue. The epithelial component was arranged in anastomosing cords, solid nests and variable-sized cysts that were lined by squamous or cuboidal epithelium. The spindle cells revealed the myoepithelial immunohistochemical phenotype. There was no obvious thymic differentiation nor was any normal thymic tissue observed in our case. We think that EHT needs to be reclassified with using different nomenclature to designate its origin and histology. Further, pathologists and clinicians should be aware of the existence of this tumor in the lower neck so as not to mistake it for high-grade sarcoma or spindle cell carcinoma.
BACKGROUND :Prostatic adenocarcinoma makes up about 2% of the total cancer incidence and cancer death in Korean men, but the incidence of this malady is continuously increasing.
So far, there have been only a few studies describing the pathologic characteristics of the prostatic adenocarcinoma in Korean patients. In this study, we analyzed 83 radical prostatectomy specimens by using mapping analysis to discover the clinico pathologic characteristics of Korean prostatic adenocarcinoma. METHODS The resected prostates were serially sectioned and embedded for histologic mapping. The clinico pathologic findings, including the Gleason score, tumor size, prostate intraepithelial neoplasia (PIN) and tumor invasion to the surrounding tissues, were examined. RESULTS The mean values were as follows: age, 64.1+/-6.6 years; serum prostate specific antigen (sPSA), 16.6+/-16.2 ng/mL; tumor volume, 22.3+/-22.4%; tumor size, 2.2+/-1.2 cm; and Gleason score, 6.9+/-0.9. The rate of high grade PIN was 79.7%. The Gleason score, tumor extent and T stage were statistically correlated (p<0.05). CONCLUSIONS Some prognostic factors such as sPSA and the Gleason scores showed significantly lower levels compared with those of the previous studies on Korean prostate adenocarcinoma (16-36 ng/mL vs 16.6 ng/mL and 7.3-7.7 vs 6.9, respectively). Although these values are still higher than those of the western studies, this study implies that the early detection of prostate adenocarcinoma is increasing in Korea.
To evaluate correlation between the amount of oncogene products in tumor cell extracts and malignant potentiality in breast tumor, immunohistochemical staining for the ras Oncogene products was performed in the sections of benign and malignant lesions of the breast. The results obtained were as follows: 1) The positive reaction to ras Oncogene products was usually observed in the cytoplasm and cell membrane. 2) The ratio of positive reaction was 30.4% in epithelial hyperplasia of fibrocystic disease, 26.5% in fibroadenoma. 49.5% in intraductal carcinoma 71.6% in infiltrating ductal carcinoma, 85.2% in metastatic infiltrating ductal carcinoma, and 89.7% in relatively preserved neighboring lobules of infiltrating ductal carcinoma. In conclusion, the ras oncogene products are found by a significantly higher ratio in the more aggressive lesions, and the infiltrating ductal carcinoma might represent its potential of malignant transformation. 3) The expression of ras oncogene was heterogeneous in primary as well as metastatic mammary carcinomas.