Journal of Pathology and Translational Medicine

Original Articles

Prognostic significance of viable tumor size measurement in hepatocellular carcinomas after preoperative locoregional treatment: Yoon Jung Hwang, Youngeun Lee, Hyunjin Park, Yangkyu Lee, Kyoungbun Lee, Haeryoung Kim; J Pathol Transl Med. 2021;55(5):338-348. Published online September 2, 2021; DOI: https://doi.org/10.4132/jptm.2021.07.26

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Background
Preoperative locoregional treatment (LRT) for hepatocellular carcinoma (HCC) often induces intratumoral necrosis without affecting the overall tumor size, and residual viable tumor size (VTS) on imaging is an important clinical parameter for assessing post-treatment response. However, for surgical specimens, it is unclear whether the VTS would be more relevant to prognosis compared to total tumor size (TTS).
Methods
A total of 142 surgically resected solitary HCC cases were retrospectively reviewed. The TTS and VTS were assessed by applying the modified Response Evaluation Criteria in Solid Tumors method to the resected specimens, and correlated with the clinicopathological features and survival.
Results
As applying VTS, 13/142 cases (9.2%) were down-staged to ypT1a. Although the survival analysis results for overall survival according to TTS or VTS were similar, VTS was superior to predict disease-free survival (DFS; p = .023) compared to TTS (p = .08). In addition, multivariate analysis demonstrated VTS > 2 cm to be an independent predictive factor for decreased DFS (p = .001). In the subpopulation of patients with LRT (n = 54), DFS in HCCs with TTS or VTS > 2 cm were significantly shorter than those with TTS or VTS ≤ 2 cm (p = .047 and p = .001, respectively). Interestingly, HCCs with TTS > 2 cm but down-staged to VTS ≤ 2 cm after preoperative LRT had similar survival to those with TTS ≤ 2 cm.
Conclusions
Although the prognostic impact of tumor size was similar regardless of whether TTS or VTS was applied, reporting VTS may help to increase the number of candidates for surgery in HCC patients with preoperative LRT.

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Evaluation of Pathologic Complete Response in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy: Experience in a Single Institution over a 10-Year Period: Misun Choi, Yeon Hee Park, Jin Seok Ahn, Young-Hyuck Im, Seok Jin Nam, Soo Youn Cho, Eun Yoon Cho; J Pathol Transl Med. 2017;51(1):69-78. Published online December 25, 2016; DOI: https://doi.org/10.4132/jptm.2016.10.05

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Abstract PDF

Background
Pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) has been associated with favorable clinical outcome in breast cancer patients. However, the possibility that the prognostic significance of pCR differs among various definitions has not been established. Methods: We retrospectively evaluated the pathologic response after NAC in 353 breast cancer patients and compared the prognoses after applying the following different definitions of pCR: ypT0/is, ypT0, ypT0/is ypN0, and ypT0 ypN0. Results: pCR was significantly associated with improved distant disease-free survival (DDFS) regardless of the definition (ypT0/is, p = .002; ypT0, p = .008; ypT0/is ypN0, p < .001; ypT0 ypN0, p = .003). Presence of tumor deposits of any size in the lymph nodes (LNs; ypN ≥ 0(i+)) was associated with worse DDFS (ypT0 ypN0 vs ypT0 ypN ≥ 0(i+), p = .036 and ypT0/is ypN0 vs ypT0/is ypN ≥ 0(i+), p = .015), and presence of isolated tumor cells was associated with decreased overall survival (OS; ypT0/is ypN0 vs ypT0/is ypN0(i+), p = .013). Residual ductal carcinoma in situ regardless of LN status showed no significant difference in DDFS or OS (DDFS: ypT0 vs ypTis, p = .373 and ypT0 ypN0 vs ypTis ypN0, p = .462; OS: ypT0 vs ypTis, p = .441 and ypT0 ypN0 vs ypTis ypN0, p = .758). In subsequent analysis using ypT0/is ypN0, pCR was associated with improved DDFS and OS in triple-negative tumors (p < .001 and p = .003, respectively). Conclusions: Based on our study results, the prognosis and rate of pCR differ according to the definition of pCR and ypT0/is ypN0 might be considered a more preferable definition of pCR.

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Review

Pathologic Evaluation of Breast Cancer after Neoadjuvant Therapy: Cheol Keun Park, Woo-Hee Jung, Ja Seung Koo; J Pathol Transl Med. 2016;50(3):173-180. Published online April 11, 2016; DOI: https://doi.org/10.4132/jptm.2016.02.02

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Abstract PDF

Breast cancer, one of the most common cancers in women, has various treatment modalities. Neoadjuvant therapy (NAT) has been used in many clinical trials because it is easy to evaluate the treatment response to therapeutic agents in a short time period; consequently, NAT is currently a standard treatment modality for large-sized and locally advanced breast cancers, and its use in early-stage breast cancer is becoming more common. Thus, chances to encounter breast tissue from patients treated with NAT is increasing. However, systems for handling and evaluating such specimens have not been established. Several evaluation systems emphasize a multidisciplinary approach to increase the accuracy of breast cancer assessment. Thus, detailed and systematic evaluation of clinical, radiologic, and pathologic findings is important. In this review, we compare the major problems of each evaluation system and discuss important points for handling and evaluating NAT-treated breast specimens.

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Original Articles

Pathologic Factors Associated with Prognosis after Adjuvant Chemotherapy in Stage II/III Microsatellite-Unstable Colorectal Cancers: Jung Ho Kim, Jeong Mo Bae, Hyeon Jeong Oh, Hye Seung Lee, Gyeong Hoon Kang; J Pathol Transl Med. 2015;49(2):118-128. Published online March 12, 2015; DOI: https://doi.org/10.4132/jptm.2015.02.05

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Abstract PDF

Background
Although there are controversies regarding the benefit of fluoropyrimidine-based adjuvant chemotherapy in patients with microsatellite instability–high (MSI-H) colorectal cancer (CRC), the pathologic features affecting postchemotherapeutic prognosis in these patients have not been fully identified yet. Methods: A total of 26 histopathologic and immunohistochemical factors were comprehensively evaluated in 125 stage II or III MSI-H CRC patients who underwent curative resection followed by fluoropyrimidine-based adjuvant chemotherapy. We statistically analyzed the associations of these factors with disease-free survival (DFS). Results: Using a Kaplan- Meier analysis with log-rank test, we determined that ulceroinfiltrative gross type (p=.003), pT4 (p<.001), pN2 (p=.002), perineural invasion (p=.001), absence of peritumoral lymphoid reaction (p=.041), signet ring cell component (p=.006), and cribriform comedo component (p=.004) were significantly associated with worse DFS in patients receiving oxaliplatin-based adjuvant chemotherapy (n=45). By contrast, pT4 (p<.001) and tumor budding-positivity (p=.032) were significant predictors of poor survival in patients receiving non-oxaliplatin–based adjuvant chemotherapy (n=80). In Cox proportional hazards regression model-based univariate and multivariate analyses, pT category (pT1-3 vs pT4) was the only significant prognostic factor in patients receiving non-oxaliplatin–based adjuvant chemotherapy, whereas pT category, signet ring cell histology and cribriform comedo histology remained independent prognostic factors in patients receiving oxaliplatin-based adjuvant chemotherapy. Conclusions: pT4 status is the most significant pathologic determinant of poor outcome after fluoropyrimidine-based adjuvant chemotherapy in patients with stage II/III MSI-H CRC.

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British Journal of Cancer.2016; 115(4): 490. CrossRef
Distinct features betweenMLH1-methylated and unmethylated colorectal carcinomas with the CpG island methylator phenotype: implications in the serrated neoplasia pathway
Jung Ho Kim, Jeong Mo Bae, Nam-Yun Cho, Gyeong Hoon Kang
Oncotarget.2016; 7(12): 14095. CrossRef
Tumor deposits: markers of poor prognosis in patients with locally advanced rectal cancer following neoadjuvant chemoradiotherapy
Lu-Ning Zhang, Wei-Wei Xiao, Shao-Yan Xi, Pu-Yun OuYang, Kai-Yun You, Zhi-Fan Zeng, Pei-Rong Ding, Hui-Zhong Zhang, Zhi-Zhong Pan, Rui-Hua Xu, Yuan-Hong Gao
Oncotarget.2016; 7(5): 6335. CrossRef

ERCC1 Predicts a Poorer Platinum-based Chemotherapy Outcome but a Better Outcome for Uracil-Tegafur in the Resected Stage I-II NSCLC.: Han Suk Ryu, Xianhua Xu, Hyojin Kim, Jong Suk Lee, Sanghoon Jheon, Jin Haeng Chung; Korean J Pathol. 2011;45(1):45-52.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.1.45

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Abstract PDF: BACKGROUND
The role of excision repair cross-complementation group 1 (ERCC1) has been controversial in non-small cell lung cancer (NSCLC) patients who received adjuvant chemotherapy with a platinum agent. We investigated ERCC1 expression in stage I-II NSCLC to clarify its significance for adjuvant chemotherapy.
METHODS
The ERCC1 expression profile was evaluated by immunohistochemistry and compared according to adjuvant chemotherapeutic agents in 146 patients who underwent surgical resection for stage I-II NSCLC. The patients were divided into 3 groups; adjuvant chemotherapy with a platinum based agent (18.5%, 27/146); adjuvant chemotherapy with uracil-tegafur (UFT) (40.4%, 59/146); surgery-alone (41.1%, 60/146).
RESULTS
Nuclear ERCC1 expression was detected in 71.9% (105/146) of NSCLC and was significantly associated with a shortened survival period in the group 1 patients who received the platinum based regimen after surgery. The group 2 patients who received UFT showed the longest survival period, followed by the surgery-alone group (overall survival, p=0.049; disease-free survival [DFS], p<0.001).
CONCLUSIONS
These results suggest that stage I-II NSCLC patients with ERCC1 expression experience a shorter DFS period with adjuvant chemotherapy with a platinum based regimen and may benefit from adjuvant chemotherapy with UFT, instead of platinum after surgery.

The Effects of Immunosuppressant and Immunostimulant on the Splenic Cell Subset of Rats Having Undergone Experimentally Induced Septal Fibrosis of Liver.: Mee Young Sol, Joon Yeon Kim, Sun Kyoung Lee; Korean J Pathol. 1995;29(5):572-583.

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Abstract: Although there have been many reports about the importance of the spleen's role in hepatic fibrogenesis, the exact mechanism is still uncertain. The author designed this study to evaluate splenic function on hepatic fibrogenesis. The degree of hepatic fibrosis and the population of splenocyte subsets were studied in the experimental animal model with fibrosis produced by injecting normal swine serum intra-peritoneally into Sprague-Dawley rats. The animals were divided into three groups; group A was subjected to injection of swine serum only, group B swine serum and complete Freund's adjuvant and group C swine serum and cyclosporin A. The experimental hepatic fibrogenesis by swine serum was augumented by coinjection with the adjuvant and inhibited by cyclosporin A. The study of the splenocyte subset revealed increased percentages of spienic B cell and CD4+ cell and a decreased percentage of CD8+ cell, and these changes of splenocyte subset were also augumented by the adjuvant and inhibited by cyclosporin A. The percent of monocytes was not significantly altered, although a tendancy of early decrease by the adjuvant was noted.

Changes in Protein Expression in Breast Cancer after Anthracycline-Based Chemotherapy.: Ho chang Lee, Jae Ok Lee, In Ae Park; Korean J Pathol. 2007;41(3):165-170.

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Abstract PDF: Background
: Anthracyclines are the standard agents used to treat patients with advanced breast carcinoma. Some molecules are reportedly associated with anthracycline resistance; however, there has been some controversy surrounding these claims. The gain or loss of certain molecules after chemotherapy can explain the discrepancies in the results.
Methods
: We evaluated the expression levels of the estrogen receptor (ER), p53, and bcl-2 in specimens obtained from twenty patients with advanced breast cancer before and after anthracyclinebased chemotherapy using immunohistochemistry (IHC). We also examined HER2/neu expression in these specimens using IHC and fluorescence in situ hybridization (FISH) analysis.
Results
: After chemotherapy, one of the twenty cases (5%) showed decreased ER expression, one (5%) showed decreased p53 expression, and one (5%) showed increased bcl-2 expression. IHC and FISH analysis in pre- and post-chemotherapy specimens showed that the expression of HER2/neu changed from equivocal to negative in one case (5%).
Conclusion
: Our results showed that the expression levels of HER2/neu, ER, p53 and bcl-2 remained stable after chemotherapy, although the statistical significance of these results may not be validated due to the small number of cases. We also suggested that the resistance to anthracycline-based chemotherapy might not be associated with the modification of these molecules.

A High Thymidylate Synthase Expression is Related to Better Outcome for Advanced Gastric Cancer Patients Treated with 5-FU Chemotherapy after Curative Resection.: Mee Yon Cho, Sang Yeop Yi, Min seob Eom, Shu Peng Zhang, Hwan Sik Kim, Jong In Lee, Dae Sung Kim; Korean J Pathol. 2006;40(2):128-136.

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Abstract PDF: BACKGROUND
The expressions of thymidylate synthase (TS), E2F-1, pRb, and p53 are correlated with DNA synthesis. The significance of their expressions is still controversial for predicting the outcome of 5-fluorouracil (5-FU) therapy in the patients with advanced gastric carcinoma. Furthermore, their prognostic value in the metastatic lesions of gastric carcinoma has not yet been confirmed.
METHODS
To ascertain their prognostic value, we immunohistochemically analyzed the expressions of TS, E2F-1, pRb, and p53 in the primary tumors and the related metastatic lymph nodes, and we then compared the survival between the high and low expression group of each protein. Ninety four patients with advanced gastric carcinoma who were treated by complete resection and adjuvant 5-FU chemotherapy were analyzed.
RESULTS
The TS expression in primary tumors was significantly correlated with that of E2F-1. The expression of these genes showed no significant difference between the primary tumors and the metastatic lymph nodes except for E2F-1, which was significantly higher in the lymph node metastasis than in the primary tumors. After complete resection and 5-FU-based adjuvant chemotherapy, patients with a high TS expression in the primary tumors showed a longer survival than those patients having primary tumors with a low TS expression (p=0.0392).
CONCLUSION
A high TS expression in the primary tumors may be related to a better outcome for advanced gastric cancer patients who were treated with 5-FU chemotherapy after curative resection.

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