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Comparison of the Mismatch Repair System between Primary and Metastatic Colorectal Cancers Using Immunohistochemistry
Jiyoon Jung, Youngjin Kang, Yoo Jin Lee, Eojin Kim, Bokyung Ahn, Eunjung Lee, Joo Young Kim, Jeong Hyeon Lee, Youngseok Lee, Chul Hwan Kim, Yang-Seok Chae
J Pathol Transl Med. 2017;51(2):129-136.   Published online February 14, 2017
DOI: https://doi.org/10.4132/jptm.2016.12.09
  • 9,063 View
  • 314 Download
  • 27 Web of Science
  • 24 Crossref
AbstractAbstract PDF
Background
Colorectal cancer (CRC) is one of the most common malignancies worldwide. Approximately 10%–15% of the CRC cases have defective DNA mismatch repair (MMR) genes. Although the high level of microsatellite instability status is a predictor of favorable outcome in primary CRC, little is known about its frequency and importance in secondary CRC. Immunohistochemical staining (IHC) for MMR proteins (e.g., MLH1, MSH2, MSH6, and PMS2) has emerged as a useful technique to complement polymerase chain reaction (PCR) analyses. Methods: In this study, comparison between the MMR system of primary CRCs and paired liver and lung metastatic lesions was done using IHC and the correlation with clinical outcomes was also examined. Results: Based on IHC, 7/61 primary tumors (11.4%) showed deficient MMR systems, while 13/61 secondary tumors (21.3%) showed deficiencies. In total, 44 cases showed proficient expression in both the primary and metastatic lesions. Three cases showed deficiencies in both the primary and paired metastatic lesions. In 10 cases, proficient expression was found only in the primary lesions, and not in the corresponding metastatic lesions. In four cases, proficient expression was detected in the secondary tumor, but not in the primary tumor. Conclusions: Although each IHC result and the likely defective genes were not exactly matched between the primary and the metastatic tumors, identical results for primary and metastatic lesions were obtained in 77% of the cases (47/61). These data are in agreement with the previous microsatellite detection studies that used PCR and IHC.

Citations

Citations to this article as recorded by  
  • MMR profile and microsatellite instability status in colorectal mucinous adenocarcinoma with synchronous metastasis: a new clue for the clinical practice
    Paola Parente, Umberto Malapelle, Valentina Angerilli, Mariangela Balistreri, Sara Lonardi, Salvatore Pucciarelli, Caterina De Luca, Francesco Pepe, Gianluca Russo, Elena Vigliar, Angela Danza, Fabio Scaramuzzi, Giancarlo Troncone, Paolo Graziano, Matteo
    Journal of Clinical Pathology.2023; 76(7): 492.     CrossRef
  • Histomorphological and molecular genetic characterization of different intratumoral regions and matched metastatic lymph nodes of colorectal cancer with heterogenous mismatch repair protein expression
    Jing Zhang, Xin Zhang, Qian Wang, Yu-yin Xu, Qian-lan Yao, Dan Huang, Wei-qi Sheng, Xiao-li Zhu, Xiao-yan Zhou, Qian-ming Bai
    Journal of Cancer Research and Clinical Oncology.2023; 149(7): 3423.     CrossRef
  • Intraindividual Tumor Heterogeneity of Mismatch Repair Status in Metastatic Colorectal Cancer
    Qianpeng Huang, Tao Yu, Lei Li, Qi Zhang, Shiyao Zhang, Baosong Li, Xiaoping Li, Wanyi Xiao, Gang Liu
    Applied Immunohistochemistry & Molecular Morphology.2023; 31(2): 84.     CrossRef
  • Patterns of DNA mismatch repair protein expression for primary and recurrent colorectal cancer at an advanced surgical unit: A retrospective audit
    Charles Risbey, Timothy Fielder, Daniel Steffens, Joo‐Shik Shin, Michael Solomon
    Colorectal Disease.2023; 25(3): 369.     CrossRef
  • Mesonephric-like Adenocarcinoma of the Uterine Corpus: Genomic and Immunohistochemical Profiling with Comprehensive Clinicopathological Analysis of 17 Consecutive Cases from a Single Institution
    Hyun-Hee Koh, Eunhyang Park, Hyun-Soo Kim
    Biomedicines.2023; 11(8): 2269.     CrossRef
  • Multilevel Heterogeneity of Colorectal Cancer Liver Metastasis
    Hao Chen, Chongya Zhai, Xian Xu, Haidong Wang, Weidong Han, Jiaying Shen
    Cancers.2023; 16(1): 59.     CrossRef
  • Heterogeneity of Mismatch Repair Status and Microsatellite Instability between Primary Tumour and Metastasis and Its Implications for Immunotherapy in Colorectal Cancers
    Camille Evrard, Stéphane Messina, David Sefrioui, Éric Frouin, Marie-Luce Auriault, Romain Chautard, Aziz Zaanan, Marion Jaffrelot, Christelle De La Fouchardière, Thomas Aparicio, Romain Coriat, Julie Godet, Christine Silvain, Violaine Randrian, Jean-Chri
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  • Clinicopathologic Factors Associated with Mismatch Repair Status Among Filipino Patients with Young-Onset Colorectal Cancer
    Dennis Lee Sacdalan, Reynaldo L Garcia, Michele H Diwa, Danielle Benedict Sacdalan
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  • Evaluating Mismatch Repair/Microsatellite Instability Status Using Cytology Effusion Specimens to Determine Eligibility for Immunotherapy
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    Archives of Pathology & Laboratory Medicine.2021; 145(1): 46.     CrossRef
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  • Identificación del fenotipo de inestabilidad microsatelital en carcinoma colorrectal mediante el análisis de la expresión de proteínas reparadoras del ADN: Revisión narrativa
    Orlando Rodas-Pernillo, Edith Oregón
    Ciencia, Tecnologí­a y Salud.2021; 8(2): 232.     CrossRef
  • Japan Society of Clinical Oncology provisional clinical opinion for the diagnosis and use of immunotherapy in patients with deficient DNA mismatch repair tumors, cooperated by Japanese Society of Medical Oncology, First Edition
    Saori Mishima, Hiroya Taniguchi, Kiwamu Akagi, Eishi Baba, Yutaka Fujiwara, Akira Hirasawa, Masafumi Ikeda, Osamu Maeda, Kei Muro, Hiroshi Nishihara, Hiroyki Nishiyama, Tadao Takano, Katsuya Tsuchihara, Yasushi Yatabe, Yasuhiro Kodera, Takayuki Yoshino
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  • Microsatellite Stable Colorectal Cancer With an Immunogenic Phenotype: Challenges in Diagnosis and Treatment
    James Saller, Dahui Qin, Seth Felder, Domenico Coppola
    Clinical Colorectal Cancer.2020; 19(2): 123.     CrossRef
  • Should you repeat mismatch repair testing in cases of tumour recurrence? An evaluation of repeat mismatch repair testing by the use of immunohistochemistry in recurrent tumours of the gastrointestinal and gynaecological tracts
    John J Aird, Michael J Steel, Christine Chow, Julie Ho, Robert Wolber, C Blake Gilks, Lynn N Hoang, David F Schaeffer
    Histopathology.2020; 76(4): 521.     CrossRef
  • Microsatellite instability as a unique characteristic of tumors and a predictor of response to immune therapy
    A.  A. Tryakin, M.  Yu. Fedyanin, A.  S. Tsukanov, Yu.  A. Shelygin, I.  A. Pokataev, E.  O. Ignatova, G.  G. Khakimova, M.  A. Frolova, S.  A. Tjulandin
    Malignant tumours.2020; 9(4): 59.     CrossRef
  • Spontaneous regression of transverse colon cancer with high-frequency microsatellite instability: a case report and literature review
    Nozomi Karakuchi, Manabu Shimomura, Kazuhiro Toyota, Takao Hinoi, Hideki Yamamoto, Seiji Sadamoto, Koichi Mandai, Hiroyuki Egi, Hideki Ohdan, Tadateru Takahashi
    World Journal of Surgical Oncology.2019;[Epub]     CrossRef
  • Biomarker concordance between primary colorectal cancer and its metastases
    D.S. Bhullar, J. Barriuso, S. Mullamitha, M.P. Saunders, S.T. O'Dwyer, O. Aziz
    EBioMedicine.2019; 40: 363.     CrossRef
  • Identification of novel pathogenic MSH2 mutation and new DNA repair genes variants: investigation of a Tunisian Lynch syndrome family with discordant twins
    Amira Jaballah-Gabteni, Haifa Tounsi, Maria Kabbage, Yosr Hamdi, Sahar Elouej, Ines Ben Ayed, Mouna Medhioub, Moufida Mahmoudi, Hamza Dallali, Hamza Yaiche, Nadia Ben Jemii, Afifa Maaloul, Najla Mezghani, Sonia Abdelhak, Lamine Hamzaoui, Mousaddak Azzouz,
    Journal of Translational Medicine.2019;[Epub]     CrossRef
  • Mismatch repair status between primary colorectal tumor and metastatic tumor, a retrospective consistent study
    Zheng Wang, Xiaoli Tang, Xiaoqing Wu, Meiyuan Yang, Daorong Wang
    Bioscience Reports.2019;[Epub]     CrossRef
  • Heterogeneity of mismatch repair defect in colorectal cancer and its implications in clinical practice
    Gaelle Tachon, Eric Frouin, Lucie Karayan-Tapon, Marie-Luce Auriault, Julie Godet, Valerie Moulin, Qing Wang, David Tougeron
    European Journal of Cancer.2018; 95: 112.     CrossRef
  • DNA mismatch repair in cancer
    Marina Baretti, Dung T. Le
    Pharmacology & Therapeutics.2018; 189: 45.     CrossRef
  • Discordant loss of mismatch repair proteins in advanced endometrial endometrioid carcinoma compared to paired primary uterine tumors
    Robert M. Ta, Jonathan L. Hecht, Douglas I. Lin
    Gynecologic Oncology.2018; 151(3): 401.     CrossRef
  • The CpG island methylator phenotype is concordant between primary colorectal carcinoma and matched distant metastases
    Stacey A. Cohen, Ming Yu, Kelsey Baker, Mary Redman, Chen Wu, Tai J. Heinzerling, Ralph M. Wirtz, Elpida Charalambous, George Pentheroudakis, Vassiliki Kotoula, Konstantine T. Kalogeras, George Fountzilas, William M. Grady
    Clinical Epigenetics.2017;[Epub]     CrossRef
Does Polymerase Chain Reaction of Tissue Specimens Aid in the Diagnosis of Tuberculosis?
Yoo Jin Lee, Seojin Kim, Youngjin Kang, Jiyoon Jung, Eunjung Lee, Joo-Young Kim, Jeong Hyeon Lee, Youngseok Lee, Yang-seok Chae, Chul Hwan Kim
J Pathol Transl Med. 2016;50(6):451-458.   Published online October 10, 2016
DOI: https://doi.org/10.4132/jptm.2016.08.04
  • 9,344 View
  • 231 Download
  • 5 Web of Science
  • 7 Crossref
AbstractAbstract PDF
Background
Mycobacterial culture is the gold standard test for diagnosing tuberculosis (TB), but it is time-consuming. Polymerase chain reaction (PCR) is a highly sensitive and specific method that can reduce the time required for diagnosis. The diagnostic efficacy of PCR differs, so this study determined the actual sensitivity of TB-PCR in tissue specimens.
Methods
We retrospectively reviewed 574 cases. The results of the nested PCR of the IS6110 gene, mycobacterial culture, TB-specific antigen-induced interferon-γ release assay (IGRA), acid-fast bacilli (AFB) staining, and histological findings were evaluated.
Results
The positivity rates were 17.6% for PCR, 3.3% for the AFB stain, 22.2% for mycobacterial culture, and 55.4% for IGRA. PCR had a low sensitivity (51.1%) and a high specificity (86.3%) based on the culture results of other studies. The sensitivity was higher (65.5%) in cases with necrotizing granuloma but showed the highest sensitivity (66.7%) in those with necrosis only. The concordance rate between the methods indicated that PCR was the best method compared to mycobacterial culture, and the concordance rate increased for the methods using positive result for PCR or histologic features.
Conclusions
PCR of tissue specimens is a good alternative to detect tuberculosis, but it may not be as sensitive as previously suggested. Its reliability may also be influenced by some histological features. Our data showed a higher sensitivity when specimens contained necrosis, which indicated that only specimens with necrosis should be used for PCR to detect tuberculosis.

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SIRT7, H3K18ac, and ELK4 Immunohistochemical Expression in Hepatocellular Carcinoma
Hye Seung Lee, Wonkyung Jung, Eunjung Lee, Hyeyoon Chang, Jin Hyuk Choi, Han Gyeom Kim, Aeree Kim, Baek-hui Kim
J Pathol Transl Med. 2016;50(5):337-344.   Published online August 5, 2016
DOI: https://doi.org/10.4132/jptm.2016.05.20
  • 9,531 View
  • 163 Download
  • 21 Web of Science
  • 23 Crossref
AbstractAbstract PDF
Background
SIRT7 is one of the histone deacetylases and is NAD-dependent. It forms a complex with ETS-like transcription factor 4 (ELK4), which deacetylates H3K18ac and works as a transcriptional suppressor. Overexpression of SIRT7 and deacetylation of H3K18ac have been shown to be associated with aggressive clinical behavior in some cancers, including hepatocellular carcinoma (HCC). The present study investigated the immunohistochemical expression of SIRT7, H3K18ac, and ELK4 in hepatocellular carcinoma.
Methods
A total of 278 HCC patients were enrolled in this study. Tissue microarray blocks were made from existing paraffin-embedded blocks. Immunohistochemical expressions of SIRT7, H3K18ac and ELK4 were scored and analyzed.
Results
High SIRT7 (p = .034), high H3K18ac (p = .001), and low ELK4 (p = .021) groups were associated with poor outcomes. Age < 65 years (p = .028), tumor size ≥ 5 cm (p = .001), presence of vascular emboli (p = .003), involvement of surgical margin (p = .001), and high American Joint Committee on Cancer stage (III&V) (p < .001) were correlated with worse prognoses. In multivariate analysis, H3K18ac (p = .001) and ELK4 (p = .015) were the significant independent prognostic factors.
Conclusions
High SIRT7 expression with poor overall survival implies that deacetylation of H3K18ac contributes to progression of HCC. High H3K18ac expression with poor prognosis is predicted due to a compensation mechanism. In addition, high ELK4 expression with good prognosis suggests another role of ELK4 as a tumor suppressor beyond SIRT7’s helper. In conclusion, we could assume that the H3K18ac deacetylation pathway is influenced by many other factors.

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Tumor Sprouting in Papillary Thyroid Carcinoma Is Correlated with Lymph Node Metastasis and Recurrence
Eunjung Lee, Wonkyung Jung, Jeong-Soo Woo, Jae Bok Lee, Bong Kyung Shin, Han Kyeom Kim, Aeree Kim, Baek-hui Kim
Korean J Pathol. 2014;48(2):117-125.   Published online April 28, 2014
DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.2.117
  • 9,779 View
  • 62 Download
  • 6 Crossref
AbstractAbstract PDF
Background

Identification of poor prognostic factors in papillary thyroid carcinoma (PTC) patients is important for the patients' care and follow-up. We can sometimes see small tumor clusters without desmoplasia and no evidence of lymphatic emboli around the main tumor mass of PTC. We termed this form of tumor clustering, 'tumor sprouting,' and determined whether these tumors correlate with lymphovascular invasion, lymph node metastasis, and recurrence.

Methods

We analyzed a total of 204 cases of papillary thyroid macrocarcinoma. Number, size and distance from the main tumor of the tumor sprouting were observed and analyzed with clinicopathologic characteristics.

Results

Tumor sprouting was observed in 101 patients. Presence of tumor sprouting was significantly associated with positive resection margin (p=.002), lymphovascular invasion (p=.001), lymph node metastasis (p<.001), and recurrence (p=.004). Univariate analysis of recurrence-free survival revealed that tumor multiplicity (p=.037), positive resection margin (p=.007), lymphovascular invasion (p=.004), lymph node metastasis (p<.001), and tumor sprouting (p=.004) were poor prognostic factors. In multivariate analysis, positive resection margin was an independent poor prognostic factor of recurrence.

Conclusions

In conclusion, tumor sprouting is significantly correlated with lymph node metastasis and recurrence. Evaluation of tumor sprouting in PTC patients could be helpful in predicting tumor recurrence or lymph node metastasis.

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SIRT1 Expression Is Associated with Good Prognosis in Colorectal Cancer
Wonkyung Jung, Kwang Dae Hong, Woon Yong Jung, Eunjung Lee, Bong Kyung Shin, Han Kyeom Kim, Aeree Kim, Baek-hui Kim
Korean J Pathol. 2013;47(4):332-339.   Published online August 26, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.4.332
  • 9,594 View
  • 68 Download
  • 38 Crossref
AbstractAbstract PDF
Background

Silent mating type information regulation 2 homolog 1 (SIRT1), an NAD+-dependent deacetylase, might act as a tumor promoter by inhibiting p53, but may also as a tumor suppressor by inhibiting several oncogenes such as β-catenin and survivin. Deleted in breast cancer 1 (DBC1) is known as a negative regulator of SIRT1.

Methods

Immunohistochemical expressions of SIRT1, DBC1, β-catenin, surviving, and p53 were evaluated using 2 mm tumor cores from 349 colorectal cancer patients for tissue microarray.

Results

Overexpression of SIRT1, DBC1, survivin, and p53 was seen in 235 (67%), 183 (52%), 193 (55%), and 190 (54%) patients, respectively. Altered expression of β-catenin was identified in 246 (70%) patients. On univariate analysis, overexpression of SIRT1 (p=0.029) and altered expression of β-catenin (p=0.008) were significantly associated with longer overall survival. Expression of SIRT1 was significantly related to DBC1 (p=0.001), β-catenin (p=0.001), and survivin (p=0.002), but not with p53. On multivariate analysis, age, tumor stage, differentiation, and expression of SIRT1 were independent prognostic factors significantly associated with overall survival.

Conclusions

SIRT1 overexpression is a good prognostic factor for colorectal cancer, and SIRT1 may interact with β-catenin and survivin rather than p53.

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Prognostic Significance of Heat Shock Protein 70 Expression in Early Gastric Carcinoma
Youngran Kang, Woon Yong Jung, Hyunjoo Lee, Wonkyung Jung, Eunjung Lee, Bong Kyung Shin, Aeree Kim, Han Kyeom Kim, Baek-hui Kim
Korean J Pathol. 2013;47(3):219-226.   Published online June 25, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.3.219
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AbstractAbstract PDF
Background

Overexpression of heat shock protein 70 (HSP70) has been observed in many types of cancer including gastric adenocarcinomas, although the exact role of HSP70 in carcinogenesis remains unclear.

Methods

The study analyzed a total of 458 radical gastrectomy specimens which were immunohistochemically stained with HSP70, p53, and Ki-67 antibodies.

Results

The study determined that the expression of HSP70 was significantly increased in early gastric cancer (EGC) compared to advanced gastric cancer (p<0.001). The HSP70 expression was correlated with well-differentiated tumor type, intestinal type of Lauren classification and the lower pT and pN stage. Negative expression of Ki-67 and p53 expression was associated with poor prognosis. The study did not find any correlation between HSP70 and p53 expression. The study determined that HSP70 expression in the EGC subgroup was associated with a poor prognosis (p=0.009), as well as negative Ki-67 expression (p=0.006), but was not associated with p53. Based on multivariate analysis, HSP70 expression (p=0.024), negative expression of Ki-67, invasion depth and lymph node metastasis were determined to be independent prognostic markers.

Conclusions

HSP70 is expressed in the early stages of gastric adenocarcinoma. In EGC, HSP70 is a poor independent prognostic marker and is correlated with a low proliferation index.

Citations

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Expression of SIRT1 and DBC1 in Gastric Adenocarcinoma
Youngran Kang, Woon Yong Jung, Hyunjoo Lee, Eunjung Lee, Aeree Kim, Baek-hui Kim
Korean J Pathol. 2012;46(6):523-531.   Published online December 26, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.6.523
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AbstractAbstract PDF
Background

Sirtuin 1 (SIRT1) and deleted in breast cancer 1 (DBC1) are known as tumor suppressor or promoter genes. This may be due to their diverse functions and interaction with other proteins. Gastric adenocarcinoma is one of the most common malignancies, but little is known about its carcinogenesis. Therefore, we investigated the association of immunohistochemical expression of SIRT1, DBC1, p53, and β-catenin and their variable clinicopathological characteristics.

Methods

We obtained samples from 452 patients who underwent gastrectomy. Tissue microarray blocks were constructed and immonohistochemical staining was performed.

Results

Expression of DBC1 and SIRT1 was associated with lower histologic grade, intestinal type of Lauren classification, and lower pT (p<0.001) and pN stage (DBC1, p=0.002; SIRT1, p<0.001). Association between absence of lymphatic invasion, and SIRT1 (p=0.001) and DBC1 (p=0.004) was observed. Cytoplasmic β-catenin expression was associated with lower histologic grade, pT, pN, tumor-node-metastasis (TNM) stage, DBC1 (p<0.001), and SIRT1 (p=0.001). Expression of SIRT1 and DBC1 was not associated with p53 (p=0.063 and p=0.060). DBC1 was an independent good prognostic factor in multivariate analysis (p=0.012).

Conclusions

SIRC1 and DBC1 can be considered to be good prognostic factors in gastric adenocarcinoma.

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Case Reports
Minimal Deviation Adenocarcinoma, Mucinous Type, of the Uterine Cervix: Report of a Case with Extensive Metastasis to the Uterine Corpus and Bilateral Adnexae.
Eundeok Chang, Eunjung Lee, Kyoungmee Kim, Okran Shin, Youngmi Ku, Heejung An, Changsuk Kang
Korean J Pathol. 2004;38(2):121-125.
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  • 14 Download
AbstractAbstract PDF
Minimal deviation adenocarcinoma is an extremely well differentiated variant of cervical adenocarcinoma, and is frequently misdiagnosed due to its benign-looking histopathological features. A 38-year-old woman was diagnosed as having had a minimal deviation adenocarcinoma in the cervix, metastasizing to the uterine body and bilateral adnexae. She had a history of right salpingo-oophorectomy 3 years ago, and was diagnosed as having a mucinous cystadenoma. Histologically, the tumor cells were so well-differentiated that they appeared to be almost the same as those of the non-neoplastic cervical glands. Similar glands were found in both ovaries and in the left fallopian tube. PAS staining showed a negative or apical positive pattern in the endocervical-like glands. Immunohistochemical studies for CEA, ER/PR, cytokeratin 20, and p53 were negative, but positive for cytokeratin 7. The HPV DNA microarray test was negative. Clinically, this proved to be an advanced, biologically aggressive disease.
Primary Adenocarcinoma of the Seminal Vesicle: A Case Report.
Eundeok Chang, Anhi Lee, Jehoon Lee, Eunjung Lee, Changsuk Kang
Korean J Pathol. 2003;37(2):141-144.
  • 1,630 View
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AbstractAbstract PDF
Primary adenocarcinoma of the seminal vesicle is an extremely rare tumor, and its prognosis has been known to be poor. Herein, we report an adenocarcinoma of the seminal vesicle. The patient was a 50-year-old man who complained of a two-month history of terminal hematuria and lower abdominal discomfort. A pelvic magnetic resonance imaging study. Indicated a seminal vesicle cyst with focal intraluminal growth. Right seminal vesiculectomy was performed. Grossly, the seminal vesicle revealed a markedly cystic change with focal, friable, intraluminal papillary growth. The intraluminal mass showed a noninvasive adenocarcinoma with a tubular and tubulopapillary pattern, accompanied by necrosis. Immunohistochemically, the tumor was positive for cytokeratin and carcinoembryonic antigen and negative for prostate specific antigen and prostatic acid phosphatase.

J Pathol Transl Med : Journal of Pathology and Translational Medicine