Journal of Pathology and Translational Medicine

Original Article

MicroRNA-374a Expression as a Prognostic Biomarker in Lung Adenocarcinoma: Yeseul Kim, Jongmin Sim, Hyunsung Kim, Seong Sik Bang, Seungyun Jee, Sungeon Park, Kiseok Jang; J Pathol Transl Med. 2019;53(6):354-360. Published online October 24, 2019; DOI: https://doi.org/10.4132/jptm.2019.10.01

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Background
Lung cancer is the most common cause of cancer-related death, and adenocarcinoma is the most common histologic subtype. MicroRNA is a small non-coding RNA that inhibits multiple target gene expression at the post-transcriptional level and is commonly dysregulated in malignant tumors. The purpose of this study was to analyze the expression of microRNA-374a (miR-374a) in lung adenocarcinoma and correlate its expression with various clinicopathological characteristics.
Methods
The expression level of miR-374a was measured in 111 formalin-fixed paraffin-embedded lung adenocarcinoma tissues using reverse transcription-quantitative polymerase chain reaction assays. The correlation between miR-374a expression and clinicopathological parameters, including clinical outcome, was further analyzed.
Results
High miR-374 expression was correlated with advanced pT category (chi-square test, p=.004) and pleural invasion (chi-square test, p=.034). Survival analysis revealed that patients with high miR-374a expression had significantly shorter disease-free survival relative to those with low miR-374a expression (log-rank test, p=.032).
Conclusions
miR-374a expression may serve as a potential prognostic biomarker for predicting recurrence in early stage lung adenocarcinoma after curative surgery.

Citations

Citations to this article as recorded by

Cell-free plasma miRNAs analysis for low invasive lung cancer diagnostics
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Advances in Molecular Oncology.2023; 10(2): 78. CrossRef
MicroRNA‑mediated regulation in lung adenocarcinoma: Signaling pathways and potential therapeutic implications (Review)
Jiye Liu, Fei Zhang, Jiahe Wang, Yibing Wang
Oncology Reports.2023;[Epub] CrossRef
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Zhanhong Wang, Xiao Zhang, Yanjun Wang, Dailing Xiao
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Review

Sentinel Lymph Node in Breast Cancer: Review Article from a Pathologist’s Point of View: Sophia K. Apple; J Pathol Transl Med. 2016;50(2):83-95. Published online January 12, 2016; DOI: https://doi.org/10.4132/jptm.2015.11.23

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Abstract PDF

Breast cancer staging, in particular N-stage changed most significantly due to the advanced technique of sentinel lymph node biopsy two decades ago. Pathologists have more thoroughly examined and scrutinized sentinel lymph node and found increased number of small volume metastases. While pathologists use the strict criteria from the Tumor Lymph Node Metastasis (TNM) Classification, studies have shown poor reproducibility in the application of American Joint Committee on Cancer and International Union Against Cancer/TNM guidelines for sentinel lymph node classification in breast cancer. In this review article, a brief history of TNM with a focus on N-stage is described, followed by innate problems with the guidelines, and why pathologists may have difficulties in assessing lymph node metastases uniformly. Finally, clinical significance of isolated tumor cells, micrometastasis, and macrometastasis is described by reviewing historical retrospective data and significant prospective clinical trials.

Citations

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Case Report

Kaposi's Sarcoma: A report of three cases.: Yeon Soo Lee, Yeong Jin Choi, Mi Kyung Jee, Seok Jin Kang, Byoung Kee Kim, Sun Moo Kim; Korean J Pathol. 1995;29(3):385-390.

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Abstract PDF: The classic type of Kaposi's sarcoma, or multifocal hemorrhagic sarcoma histologically characterized by proliferating fibroblastic and microvascular elements was described by Kaposi as a relatively rare neoplasm. During the past nine years, we experienced three cases of sporadic, classic Kaposi's sarcomas. They were presented as multiple papules, macules and nodules on the skin of the hands, lower logs and feet without systemic involvement. Histologically, Kaposi's sarcoma is divided into three stages, early patch, plaque and nodular stages. The nodular lesions(case 1, 2 and 3) showed extensive proliferatiion of spindle shaped, somewhat pleomorphic cells having dark prominent nuclei, proliferation of small vessels with solid aggregates of endothelial cells, and extravasation of erythrocytes. In early patch stage(case 3), widely dilated, anastomosing, thin-walled vascular spaces are noted in the upper half of the dermis. In plaque stage(case I and 3), there are proliferation of spindle shaped cells with extravasated erythrocytes and aggregates of blood vessels lined by prominent endothelial cells.

Original Articles

Immunohistochemical Analysis of TGF-beta Expression and Angiogenesis in Infiltrating Duct Carcinoma of the Breast.: Tae Jin Lee, Nam Bok Cho, Eun Sub Park, Jae Hyung Yoo, Sung Jun Park; Korean J Pathol. 1996;30(7):557-569.

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Abstract PDF: Forty cases of infiltrating duct carcinoma of the breast were examined immunohistochemically for expression of TGF-beta and angiogenesis in order to analyze significant correlation with prognostic parameters including tumor size, axillary lymph node metastasis, clinical stage, histologic grade, estrogen receptor and progesterone receptor status. The TGF-beta expression was observed in tumors center and advancing edges of tumors. To determine microvessel density for angiogenesis, we stained endothelial cells for Factor VIII related antigen and counted microvessel within tumor. The results were as follows: 1) The strong immunohistochemical expression of TGF-beta and higher counts of microvessels were observed in advancing edges of tumors (p<0.05). 2) The TGF-beta expression in the advancing edges of tumors was closely related to clinical stage and presence of axillary lymph node metastasis (p<0.05). 3) The mean microvessel counts were significantly higher in tumors from patients with axillary lymph node metastasis and increased with increasing clinical stage (p<0.05). 4) The TGF-beta expression was not related to histologic grade, estrogen receptor and progesterone receptor status(p>0.05). Therefore, the results suggested that the TGF-beta expression and angiogenesis in infiltrating duct carcinoma of the breast may play an important part in prognostic factors, closely related to the lymph node metastasis and clinical stage.

A Study on the Expression of p53 Oncogene Products, PCNA Index and DNA Ploidy in Renal Cell Carcinoma.: Jong Jae Jung, Ji Shin Lee, Chan Choi; Korean J Pathol. 1997;31(7):672-682.

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Abstract PDF: Mutant p53 is associated with the advanced stages of some human tumor but there is a wide variation in the reported incidence of p53 mutation in renal cell carcinoma and its prognostic significances. We designed this study to assess the expression of p53 in renal cell carcinomas and to compare with the established prognostic factors. Immunoreactivity for p53 protein and proliferating cell nuclear antigen (PCNA) were assessed in 44 cases of primary renal cell carcinoma, and flow cytometric analysis of DNA ploidy was perfon-ned in 37 of those cases. p53 protein was over-expressed in 16/44 (36.4%) renal cell carcinomas and 5 rumors had more than 10 immunoreactive tumor cells. The expression of p53 protein was positively related to nuclear grade (p=0.007) and PCNA index (p=0.002), but was independent of stage and DNA ploidy. In univariate survival analysis, stage (p<0.001), nuclear grade (p=0.017), DNA ploidy (p=0.045) and PCNA index (p<0.001) were significantly associated with patient survival. However, considering the stage, all of the last three factors had no prognostic influence. Cases showing strong positivity of p53 expression had worse prognosis than those with no or weak p53 expression, especially in early lesions (stage I,II) (p<0.001).

Pathology of Chronic Interstitial Lung Disease.: Dong Hwan Shin; Korean J Pathol. 1998;32(1):1-8.

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Abstract PDF: Interstitial lung disease is a generic term for a heterogeneous group of lung disease that primarily affect the interstitium although the disease is not clearly restricted to the interstitium. The majority of interstitial lung diseases represent inflammatory insults to the microscopic anatomic space bounded by the basement membrane of epithelial and endothelial cells, which may occur as slowly developing process and ultimately end up as end-stage honeycomb fibrosis. The currently prevalent classification of interstitial pneumonia with practical utility and easy reproducibility pertaining only to idopathic interstitial pneumonia encompasses several different entities some of which may represent different aspects of the same condition. Honeycomb fibrosis is usually caused by a variety of pulmonary disease including chronic interstitial lung disease. It is important to recognize that usual inter-stitial pneumonia and honeycomb fibrosis are not synonymous. In the era of chemotherapy for malignant tumor, aggressive immunosuppression for autoimmune diseases and transplant recipients and acquired immunodeficiency syndrome, lung disease in the immunocompromised host has been common. Diagnostic lung biopsy becomes increasingly needed because proper treatment of interstitial lung disease relies on correct morphologic diagnosis. This review summarizes the pathologic spectrum of idiopathic interstitial pneumonias together with other inflammatory process with known or suggestive etiologies simulating interstitial pneumonias.

Expression of Proliferating Cell Nuclear Antigen and p53 Protein in Ovarian Epithelial Tumors.: Jong Jae Jung, Jong Hee Nahm, Chang Soo Park; Korean J Pathol. 1998;32(3):193-200.

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Abstract PDF: p53 gene mutation is commonly accepted to be associated with loss of negative cell cycle control and progression of tumors. The proliferative activity of tumor cells is considered to be a valuable indicator of tumor aggressiveness. This study is intended to compare p53 protein expression with cell proliferation rates in the ovarian epithelial tumors according to the various clinicopathological parameters. Immunohistochemistry using monoclonal p53 antibody (DO-1) and PCNA antibody (PC10) was applied to 56 cases of ovarian epithelial tumors including 17 cases of borderline tumor. The results were as follows. Both immunohistochemical staining of PCNA and p53 protein showed positive reactions confined to the nuclei of tumor cells. There were significant differences of p53 protein expression rates between borderline malignancies (11.8%) and cystadenocarcinomas (56.4%) of ovary. The expression rate of p53 protein was not significantly different according to the differentiation and the stage, but the cases of strong positive reaction to p53 protein were more frequently noted in the poorly differentiated and advanced staged tumors. The PCNA indices of p53 strong positive cases were higher than those of p53 weak positive cases. In summary, p53 protein and PCNA expression may be used as an adjuvant in differentiating borderline lesions from carcinomas of ovary and predicting their biological behaviors.

nm23 Protein Immunohistochemical Expression in Colorectal Carcinoma and its Relationship with Other Prognostic Factors.: Shi Nae Lee, Heasoo Koo, Woon Sup Han; Korean J Pathol. 1998;32(6):413-419.

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Abstract: The purpose of this study was to determine the immunohistochemical expression of nm23-H1, a putative metastatic suppressor gene, and to correlate its expression with clinicopathologic variables in 75 cases of surgically resected colorectal carcinomas. There appeared to be a trend between increasing relative nm23 protein expression and Dukes' stage, vessel invasion, and metastasis of lymph nodes. nm23 was expressed in 67 cases (89.3%) and increased in cases with lower Dukes' stage (P<0.05) and in cases without vessel invasion (P<0.01) or lymph node metastasis (P<0.01). No significant relationship was observed between the nm23 protein expression and other parameters, such as tumor size, location and differentiation of the tumor. The results suggest that the nm23 protein expression plays a role in the suppression of nodal metastasis and vessel invasion in colorectal carcinomas.

Histological Grading and Staging of Chronic Hepatitis Standardized Guideline Proposed by the Korean Study Group for the Pathology of Digestive Diseases .: Young Nyun Park, Ho guen Kim, Chae Yoon Chon, Jae Bok Park, Jin Hee Sohn, Seung Ha Yang, Eun Sil Yu, Mi Seon Lee, Ja June Jang, Hee Kyung Chang, Jong Jae Jeong, Dae Young Kang, Yong Il Kim, Chan Il Park; Korean J Pathol. 1999;33(5):337-346.

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Abstract PDF: The terms chronic active hepatitis (CAH), chronic persistent hepatitis (CPH), and chronic lobular hepatitis (CLH) should be discontinued in favor of etiologic terminology. The activity of necro-inflammation and the degree of fibrosis should be evaluated for grading the severity and for the stage of disease. Members of the Korean Study Group for the Pathology of Digestive Diseases reviewed 30 cases of chronic hepatitis and reached the following consensus: 1) The pathology report of the biopsy samples with features of chronic hepatitis should include the etiology, grade and stage. 2) Grade and stage should be semiquantitatively evaluated as none, minimal, mild, moderate and severe. 3) For grading, lobular activity and periportal activity should be evaluated, separately. 4) To avoid confusion with other grading systems, simple report using descriptive terms rather than numerical records is recommended in daily practice. Criteria for each grade and stage should be presented and discussed. Histologic grading and staging of chronic hepatitis by new standardized guidelines will give more information about the prognosis as well as the present status of hepatitis. The terms CAH, CPH and CLH may be used in parentheses to facilitate relearning.

Tumor Angiogenesis and Stage in Ovarian Carcinoma.: Eun Sook Chang, Hyun Chang Joo, Tae Sung Lee; Korean J Pathol. 1999;33(8):596-602.

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Abstract PDF: Tumor angiogenesis has been found to have prognostic significance in many tumor types for predicting an increased risk of metastasis. We assessed tumor vascularity in 28 cases of borderline malignancy and 71 cases of carcinoma of the ovary which had been resected and diagnosed, using the highly specific endothelial cell marker CD34. The numbers of microvessels were counted in 200 magnification in three highly vascularised areas. The numbers of microvessels in carcinomas were higher than that in the borderline malignancy of serous and mucinous tumors. The number of microvessels of mucinous carcinomas was significantly higher than that of serous carcinomas. There were neither significant differences in the number of microvessels according to histological tumor types (p=0.075) nor significant differences in the number of microvessels according to FIGO stages (p=0.072). But in serous carcinomas, the number of microvessels was higher in the FIGO III-IV stage than in the FIGO I-II stage (p=0.017). This study showed higher neovascularization in malignant tumor than borderline malignancy, and in the advanced stage (FIGO III-IV) than less advanced stage (FIGO I-II) of serous carcinomas.

Correlation of Clinical Stage and Presumptive Prognostic Factors in Renal Cell Carcinoma.: Jin Ye Yoo, Hye Jae Cho; Korean J Pathol. 1999;33(11):1061-1066.

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Abstract PDF: Renal cell carcinoma is the most common primary cancer of the kidney. The tumor stage is a reliable prognostic marker in renal cell carcinoma which is significantly associated with patient survival. But assessment of other prognostic factors has produced varying and often conflicting results. We reevaluated the significance of varied prognostic parameters in 33 cases of renal cell carcinoma; clinical stage, cell type, histologic pattern, DNA ploidy, Ki-67 labeling index, and bcl-2 oncoprotein expression. We could not statistically prove that DNA ploidy and bcl-2 expression were related to any examined parameters. Cell type was not related to clinical stage nor nuclear grade but there was a significant correlation (p=0.002) between cell type and histologic pattern. Nuclear grade (p=0.007) and Ki-67 labeling index (p=0.036) were significantly related to clinical stage, suggesting their value as complementary prognostic markers for renal cell carcinoma.

Clinicopathologic Features of Prostatic Adenocarcinoma: A Study of 58 Radical Prostatectomy Specimens.: Tae Jin Lee, Mi Sun Choe, Choung Soo Kim, Jae Y Ro; Korean J Pathol. 1999;33(11):1067-1075.

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Abstract PDF: Prostatic carcinoma is the most commonly diagnosed cancer in the United States in men. Prostatic carcinoma in Korean men is uncommon and accounts for less than 1% of total cancer: however, the incidence of prostatic carcinoma is continuously increasing. Several clinicopathologic parameters including stage, Gleason score, and serum PSA level have been widely accepted as well established prognostic factors. To study the clinicopathologic features of prostatic carcinoma in Korean men, 58 cases of prostatic carcinoma, which were diagnosed on radical prostatectony specimens at Asan Medical Center from Jan. 1993 to June 1998 (1993; 3 cases, 1994; 3, 1995; 6, 1996; 12, 1997; 24, 1998; 10), were evaluated. The prostatic carcinomas were divided into three groups according to Gleason score. Tumors with Gleason score 6 or lower, 7, and 8 to 10 were categorized as low-grade, intermediate-grade and high-grade tumor, respectively. The overall mean age of the patients was 62.6 years (range, 4 6~76 years); mean age was 65.4, 62.8 and 61.1 in low, intermediate and high-grade tumor, respectively (p>0.05). The overall mean serum PSA level was 38.6 ng/ml (range, 0.3~276.0 ng/ml); mean serum PSA level was 17.0, 29.0 and 60.9 ng/ml in low, intermediate and high-grade tumor, respectively (p=0.002). The mean T stage was 2.3, 2.4 and 3.1 in low, intermediate and high-grade tumor (p=0.001). The percentage of positive resection margin was 33.3, 50.0 and 91.0 % in low, intermediate and high-grade tumor (p=0.001). The overall presence of prostatic intraepithelial neoplasia (PIN) was 79.3 %; percentage of the presence of PIN was 100, 79.2 and 68.2 % in low, intermediate and high-grade tumor (p>0.05). As reported in the literature, our results indicated that Gleason score was a good predictor of stage and prognosis. The higher Gleason score, the more cases were with positive surgical margins, advanced pathologic stage, and high serum PSA level (p<0.05).

Relationship among the Expression of Cyclin D1, p21, and p53 Protein, and Prognosis in Non-Small Cell Lung Carcinomas.: Seok Woo Yang, Sang Ho Cho, Woo Ick Yang, Woo Hee Jung, Chul Min Ahn, Doo Yun Lee; Korean J Pathol. 1999;33(12):1120-1130.

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Abstract PDF: Recently, cell cycle regulators have been suggested as new prognostic factors of the lung cancer. In this study, we evaluated the expression of cyclin D1, p21, and p53 using the X2-test, with regard to the stage of the patients, histologic type, and histologic differentiation in the 135 cases of non-small cell lung carcinomas (NSCLC). To evaluate the confounding effects among cyclin D1, p21, and p53 on X2-test analysis, we used the Mantel-Haenzel test. The NSCLC in this study included 82 cases of squamous cell carcinoma and 53 cases of adenocarcinoma. Each nuclear staining of cyclin D1, p21, and p53 was observed in 65 cases (48.1%), in 54 cases (40.0%), and in 81 cases (60.0%) of NSCLCs, respectively. Only p53 expression was significantly associated with the stage (stage I, II, IIIa) (p<0.05) and squamous cell carcinoma (p<0.05). On the other hand, cyclin D1 expression was significantly associated with the histologic differentiation. The confounding effects among cyclin D1, p21, and p53 revealed that only p21 expression changed the relationship between p53 and stage. In this regard, further study is needed.

Results of Sputum Cytology in Diagnosis of Lung Cancer: Based on the Results Obtained for 16 months in Presbyterian Medical Center.: Hye Kyung Lee, Kwang Min Lee, Dong Kyu Chung, Dae Song Kang, Kwi Wan Kim; Korean J Cytopathol. 1994;5(2):148-153.

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Abstract PDF: A prospective survey of sputum cytologic specimen was performed for 16 months from Jan. 1993 to Apr. 1994 in Presbyterian Medical Center. The purpose of this study is to find the positive rate of sputum cytology in the diagnosis of lung cancer and to correlate these results with tumor location and stage. Sputum cytologic specimen were received from 104 patients among 168 patients diagnosed as lung malignancy by histologic examination. Cytologic diagnosis of "suggestive of malignancy" was made in 61 patient(59%) and dysplasia in 9 patients(9%), atypia in 14 patients(13%), benign in 15 patients(14%) and inadequate specimen in 5 patients(5%), respectively. Among 84 patients beyond the cytologic diagnosis of atypia, 51 patients(61%) disclosed a central location, while 33patients(39%) showed peripheral lesions. All 54 patients diagnosed as suggestive of non-small cell carcinoma were stage III or over, and all 7 patients diagnosed as suggestive of small cell carcinoma were in advanced stage.

Histological Grade of Prostatic Adenocarcinoma.: Kyong Ho Kim, Soon Hee Jung, Chan Il Park; Korean J Pathol. 1990;24(3):236-242.

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Abstract PDF: The authors attempted to choose what has the best reproducibility and predictability for prognosis of the prostatic adenocarcinoma among four most widely used gradings methods; the Gleason's Mostofi's, Bocking and MD Anderson hospital systems. According to these gradings systems, each of two pathologists made histologic gradings of 40 consecutive prostatic adenocarcinomas which had been diagnosed with the surgically resected specimens. Correlation between the histological grades and the clinical stages was studied and a comparison was made among each system. For the comparison, the Gleason's and MDAH systems were revised as 3 grades and adjusted to the other gradings systems. In this study, MDAH grading system yielded the highest reproducibility as represented by 90% agreement, as compared with the other systems which showed 82.5~87.5% agreement. By the Gleason's, Mostofi's and Bocking's systems, 46.2%, 23.1% and 46.2% of grade 3 tumors respectively fell under the clinical stage A. On the contrary, there were no cases of grade 3 in stage A and no cases of grade 1 in stage D, by MDAH gradings system. These results suggest that MDAH gradings system is superior to the other systems in reproducibility and for predicting the biological behavior.

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