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Volume 50(5); September 2016
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Original Articles
Clinicopathologic Correlations of E-cadherin and Prrx-1 Expression Loss in Hepatocellular Carcinoma
Kijong Yi, Hyunsung Kim, Yumin Chung, Hyein Ahn, Jongmin Sim, Young Chan Wi, Ju Yeon Pyo, Young-Soo Song, Seung Sam Paik, Young-Ha Oh
J Pathol Transl Med. 2016;50(5):327-336.   Published online August 31, 2016
DOI: https://doi.org/10.4132/jptm.2016.06.22
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AbstractAbstract PDF
Background
Developing predictive markers for hepatocellular carcinoma (HCC) is important, because many patients experience recurrence and metastasis. Epithelial to mesenchymal transition (EMT) is a developmental process that plays an important role during embryogenesis and also during cancer metastasis. Paired-related homeobox protein 1 (Prrx-1) is an EMT inducer that has recently been introduced, and its prognostic significance in HCC is largely unknown.
Methods
Tissue microarray was constructed using surgically resected primary HCCs from 244 cases. Immunohistochemical staining of E-cadherin and Prrx-1 was performed. The correlation between E-cadherin loss and Prrx-1 expression, as well as other clinicopathologic factors, was evaluated.
Results
E-cadherin expression was decreased in 96 cases (39.4%). Loss of E-cadherin correlated with a higher recurrence rate (p < .001) but was not correlated with patient’s survival. Thirty-two cases (13.3%) showed at least focal nuclear Prrx-1 immunoreactivity while all non-neoplastic livers (n = 22) were negative. Prrx-1 expression was not associated with E-cadherin loss, survival or recurrence rates, pathologic factors, or the Ki-67 labeling index. Twenty tumors that were positive for E-cadherin and Prrx-1 had significantly higher nuclear grades than the rest of the cohort (p = .037). In Cox proportional hazard models, E-cadherin loss and large vessel invasion were independent prognostic factors for shorter disease-free survival. Cirrhosis and high Ki-67 index (> 40%) were independent prognostic factors for shorter overall survival.
Conclusions
Prrx-1 was expressed in small portions of HCCs but not in normal livers. Additional studies with a large number of Prrx-1-positive cases are required to confirm the results of this study.
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
  • 7,834 View
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  • 14 Citations
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.
Differential Immunohistochemical Profiles for Distinguishing Prostate Carcinoma and Urothelial Carcinoma
Woo Jin Oh, Arthur Minwoo Chung, Jee Soon Kim, Ji Heun Han, Sung Hoo Hong, Ji Yeol Lee, Yeong Jin Choi
J Pathol Transl Med. 2016;50(5):345-354.   Published online August 7, 2016
DOI: https://doi.org/10.4132/jptm.2016.06.14
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  • 19 Citations
AbstractAbstract PDF
Background
The pathologic distinction between high-grade prostate adenocarcinoma (PAC) involving the urinary bladder and high-grade urothelial carcinoma (UC) infiltrating the prostate can be difficult. However, making this distinction is clinically important because of the different treatment modalities for these two entities.
Methods
A total of 249 patient cases (PAC, 111 cases; UC, 138 cases) collected between June 1995 and July 2009 at Seoul St. Mary’s Hospital were studied. An immunohistochemical evaluation of prostatic markers (prostate-specific antigen [PSA], prostate-specific membrane antigen [PSMA], prostate acid phosphatase [PAP], P501s, NKX3.1, and α-methylacyl coenzyme A racemase [AMACR]) and urothelial markers (CK34βE12, p63, thrombomodulin, S100P, and GATA binding protein 3 [GATA3]) was performed using tissue microarrays from each tumor.
Results
The sensitivities of prostatic markers in PAC were 100% for PSA, 83.8% for PSMA, 91.9% for PAP, 93.7% for P501s, 88.3% for NKX 3.1, and 66.7% for AMACR. However, the urothelial markers CK34βE12, p63, thrombomodulin, S100P, and GATA3 were also positive in 1.8%, 0%, 0%, 3.6%, and 0% of PAC, respectively. The sensitivities of urothelial markers in UC were 75.4% for CK34βE12, 73.9% for p63, 45.7% for thrombomodulin, 22.5% for S100P, and 84.8% for GATA3. Conversely, the prostatic markers PSA, PSMA, PAP, P501s, NKX3.1, and AMACR were also positive in 9.4%, 0.7%, 18.8%, 0.7%, 0%, and 8.7% of UCs, respectively.
Conclusions
Prostatic and urothelial markers, including PSA, NKX3.1, p63, thrombomodulin, and GATA3 are very useful for differentiating PAC from UC. The optimal combination of prostatic and urothelial markers could improve the ability to differentiate PAC from UC pathologically.
Difference of the Nuclear Green Light Intensity between Papillary Carcinoma Cells Showing Clear Nuclei and Non-neoplastic Follicular Epithelia in Papillary Thyroid Carcinoma
Hyekyung Lee, Tae Hwa Baek, Meeja Park, Seung Yun Lee, Hyun Jin Son, Dong Wook Kang, Joo Heon Kim, Soo Young Kim
J Pathol Transl Med. 2016;50(5):355-360.   Published online August 22, 2016
DOI: https://doi.org/10.4132/jptm.2016.05.19
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AbstractAbstract PDF
Background
There is subjective disagreement regarding nuclear clearing in papillary thyroid carcinoma. In this study, using digital instruments, we were able to quantify many ambiguous pathologic features and use numeric data to express our findings.
Methods
We examined 30 papillary thyroid carcinomas. For each case, we selected representative cancer cells showing clear nuclei and surrounding non-neoplastic follicular epithelial cells and evaluated objective values of green light intensity (GLI) for quantitative analysis of nuclear clearing in papillary thyroid carcinoma.
Results
From 16,274 GLI values from 600 cancer cell nuclei and 13,752 GLI values from 596 non-neoplastic follicular epithelial nuclei, we found a high correlation of 94.9% between GLI and clear nuclei. GLI between the cancer group showing clear nuclei and non-neoplastic follicular epithelia was statistically significant. The overall average level of GLI in the cancer group was over two times higher than the non-neoplastic group despite a wide range of GLI. On a polygonal line graph, there was a fluctuating unique difference between both the cancer and non-neoplastic groups in each patient, which was comparable to the microscopic findings.
Conclusions
Nuclear GLI could be a useful factor for discriminating between carcinoma cells showing clear nuclei and non-neoplastic follicular epithelia in papillary thyroid carcinoma.
CD99 Is Strongly Expressed in Basal Cells of the Normal Adult Epidermis and Some Subpopulations of Appendages: Comparison with Developing Fetal Skin
Gawon Choi, Jin Roh, Chan-Sik Park
J Pathol Transl Med. 2016;50(5):361-368.   Published online August 7, 2016
DOI: https://doi.org/10.4132/jptm.2016.06.19
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  • 5 Citations
AbstractAbstract PDF
Background
CD99 is a cell surface transmembrane glycoprotein expressed in various tissues. CD99 is differentially expressed between subpopulations of each tissue and is highly expressed in certain hematopoietic and precursor cells. However, there has been no comprehensive study of CD99 expression in normal skin. We evaluated CD99 expression in normal human skin and developing fetal skin.
Methods
Seventy-five adult skin samples containing normal skin and eight fetal skin samples of different gestational ages were collected. CD99 immunohistochemical staining was performed to evaluate expression pattern in adult and fetal skin samples. CD99 and CD34 expression were compared by double immunofluorescence.
Results
In normal adult skin, CD99 was strongly expressed in the membrane of epidermal basal keratinocytes, hair follicle bulges and outer root sheaths, and inner secretory cells of eccrine sweat glands. In fetal skin, CD99 was not expressed on the periderm at 16 weeks of gestation but was expressed in basal cells of fetal skin at around 19 weeks of gestation. CD99 expression became comparable to that of the adult skin after 20 weeks of gestation. CD99 and CD34 were co-expressed in hair follicle outer root sheaths, as seen by double immunofluorescence study.
Conclusions
This is the first study examining CD99 expression pattern in normal adult and fetal skin. CD99 tends to be expressed in the basal/precursor cells of epidermis and in hair follicles. These results provide a basis for future investigation on functions of CD99 in the skin and provide a novel potential target for the treatment of dermatologic lesions.
Long Non-coding RNA HOTAIR Expression in Diffuse Large B-Cell Lymphoma: In Relation to Polycomb Repressive Complex Pathway Proteins and H3K27 Trimethylation
Eun Ji Oh, Soo Hee Kim, Woo Ick Yang, Young Hyeh Ko, Sun Och Yoon
J Pathol Transl Med. 2016;50(5):369-376.   Published online August 22, 2016
DOI: https://doi.org/10.4132/jptm.2016.06.06
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  • 20 Citations
AbstractAbstract PDF
Background
A long non-coding RNA hox transcript antisense intergenic RNA (HOTAIR) is involved in epigenetic regulation through chromatin remodeling by recruiting polycomb repressive complex 2 (PRC2) proteins (EZH2, SUZ12, and EED) that induce histone H3 trimethylation at lysine 27 (H3K27me3). Deregulation of c-MYC and interaction between c-MYC and EZH2 are well known in lymphomagenesis; however, little is known about the expression status of HOTAIR in diffuse large B-cell lymphomas (DLBCLs).
Methods
The expression status of PRC2 (EZH2, SUZ12, and EED), H3K27me3, c-MYC, and BCL2 was analyzed using immunohistochemistry (n = 231), and HOTAIR was investigated by a quantification real-time polymerase chain reaction method (n = 164) in DLBCLs.
Results
The present study confirmed the positive correlation among PRC2 proteins, H3K27me3, and c-MYC in DLBCLs. Expression level of HOTAIR was also positively correlated to EZH2 (p < .05, respectively). Between c-MYC and HOTAIR, and between c- MYC/BCL2 co-expression and HOTAIR, however, negative correlation was observed in DLBCLs (p < .05, respectively). High level of H3K27me3 was determined as an independent prognostic marker in poor overall survival (hazard ratio, 2.0; p = .023) of DLBCL patients. High expression of HOTAIR, however, was associated with favorable overall survival (p = .004) in the univariate analysis, but the impact was not significant in the multivariate analysis. The favorable outcome of DLBCL with HOTAIR high expression levels may be related to the negative correlation with c- MYC expression or c-MYC/BCL2 co-expression.
Conclusions
HOTAIR expression could be one of possible mechanisms for inducing H3K27me3 via EZH2-related PRC2 activation, and induced H3K27me3 may be strongly related to aggressive DLBCLs which show poor patient outcome.
Do Helper T Cell Subtypes in Lymphocytic Thyroiditis Play a Role in the Antitumor Effect?
Seok Woo Yang, Seong-Ho Kang, Kyung Rae Kim, In Hong Choi, Hang Seok Chang, Young Lyun Oh, Soon Won Hong
J Pathol Transl Med. 2016;50(5):377-384.   Published online September 15, 2016
DOI: https://doi.org/10.4132/jptm.2016.07.25
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  • 3 Citations
AbstractAbstract PDF
Background
Papillary thyroid carcinoma (PTC) is frequently accompanied by lymphocytic thyroiditis (LT). Some reports claim that Hashimoto’s thyroiditis (the clinical form of LT) enhances the likelihood of PTC; however, others suggest that LT has antitumor activity. This study was aimed to find out the relationship between the patterns of helper T cell (Th) cytokines in thyroid tissue of PTC with or without LT and the clinicopathological manifestation of PTC.
Methods
Fresh surgical samples of PTC with (13 cases) or without (10 cases) LT were used. The prognostic parameters (tumor size, extra-thyroidal extension of PTC, and lymph node metastasis) were analyzed. The mRNA levels of two subtypes of Th cytokines, Th1 (tumor necrosis factor α [TNF-α], interferon γ [IFN-γ ], and interleukin [IL] 2) and Th2 (IL-4 and IL-10), were analyzed. Because most PTC cases were microcarcinomas and recent cases without clinical follow-up, negative or faint p27 immunoreactivity was used as a surrogate marker for lymph node metastasis.
Results
PTC with LT cases showed significantly higher expression of TNF-α (p = .043), IFN-γ (p < .010), IL-4 (p = .015) than those without LT cases. Although the data were not statistically significant, all analyzed cytokines (except for IL-4) were highly expressed in the cases with higher expression of p27 surrogate marker.
Conclusions
These results indicate that mixed Th1 (TNF-α, IFN-γ , and IL-2) and Th2 (IL-10) immunity might play a role in the antitumor effect in terms of lymph node metastasis.
Case Studies
Mammary-Type Myofibroblastoma: A Report of Two Cases
Soyeon An, Joon Seon Song, Soonchan Park, Jung Won Lee, Kyung-Ja Cho
J Pathol Transl Med. 2016;50(5):385-389.   Published online June 6, 2016
DOI: https://doi.org/10.4132/jptm.2016.03.26
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  • 7 Citations
AbstractAbstract PDF
Mammary-type myofibroblastoma (MFB) is a rare, benign spindle cell neoplasm occurring along the milkline, with extension from the mid-axilla to the medial groin. It is histologically and immunohistochemically identical to MFB of the breast and is part of a spectrum of lesions that includes spindle cell lipoma and cellular angiofibroma. Recently, we experienced two cases of mammary-type MFB involving male patients aged 30 and 58 years, respectively. The tumors were located in the right scrotal sac and in the right axilla. Wide excisions were performed. Microscopically, the masses were composed of haphazardly arranged, variably sized fascicles of bland spindle cells and were admixed with mature fat tissue. The spindle cells in both cases showed immunopositivity for desmin and CD34 and negativity for smooth muscle actin. Loss of retinoblastoma (RB)/13q14 loci is a characteristic genetic alteration of mammary-type MFB, and we identified loss of RB protein expression by immunohistochemical staining. We emphasize the importance of awareness of this rare neoplasm when a spindle cell neoplasm is accompanied by desmin immunopositivity. The second patient was alive without recurrence for 20 months, and the first patient had not been followed.
Pulmonary Arteriovenous Fistula: Clinical and Histologic Spectrum of Four Cases
Soomin Ahn, Joungho Han, Hong Kwan Kim, Tae Sung Kim
J Pathol Transl Med. 2016;50(5):390-393.   Published online May 9, 2016
DOI: https://doi.org/10.4132/jptm.2016.04.18
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  • 5 Citations
AbstractAbstract PDF
Pulmonary arteriovenous fistula (PAVF) is abnormally dilated vessels that provide a right-to-left shunt between pulmonary artery and pulmonary vein and is clinically divided into simple and complex type. Here, we report four cases of surgically resected sporadic PAVFs presenting various clinical and histologic spectrums. Cases 1 (a 57-old-female) and 2 (a 54-old-female) presented as incidentally identified single aneurysmal fistulas and the lesions were surgically removed without complication. On the other hand, case 3 (an 11-old-male) showed diffuse dilated vascular sacs involving both lungs and caused severe hemodynamic and pulmonary dysfunction. Embolization and surgical resection of the main lesion failed to relieve the symptoms. Case 4 (a 36-old-male) had a localized multiloculated cyst clinically mimicking congenital cystic adenomatoid malformation. Microscopically, the lesion consisted of dilated thick vessels, consistent with the diagnosis of fistulous arteriovenous malformation/hemangioma.
Nodular Fasciitis of External Auditory Canal
Jihyun Ahn, Sunyoung Kim, Youngsil Park
J Pathol Transl Med. 2016;50(5):394-396.   Published online June 6, 2016
DOI: https://doi.org/10.4132/jptm.2016.03.11
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  • 1 Citations
AbstractAbstract PDF
Nodular fasciitis is a pseudosarcomatous reactive process composed of fibroblasts and myofibroblasts, and it is most common in the upper extremities. Nodular fasciitis of the external auditory canal is rare. To the best of our knowledge, less than 20 cases have been reported to date. We present a case of nodular fasciitis arising in the cartilaginous part of the external auditory canal. A 19-year-old man complained of an auricular mass with pruritus. Computed tomography showed a 1.7 cm sized soft tissue mass in the right external auditory canal, and total excision was performed. Histologic examination revealed spindle or stellate cells proliferation in a fascicular and storiform pattern. Lymphoid cells and erythrocytes were intermixed with tumor cells. The stroma was myxoid to hyalinized with a few microcysts. The tumor cells were immunoreactive for smooth muscle actin, but not for desmin, caldesmon, CD34, S-100, anaplastic lymphoma kinase, and cytokeratin. The patient has been doing well during the 1 year follow-up period.
Brief Case Reports
Pelvic Nodular Histiocytic and Mesothelial Hyperplasia in a Patient with Endometriosis and Uterine Leiomyoma
Yumin Chung, Rehman Abdul, Se Min Jang, Joong Sub Choi, Kiseok Jang
J Pathol Transl Med. 2016;50(5):397-400.   Published online April 4, 2016
DOI: https://doi.org/10.4132/jptm.2016.01.11
  • 6,643 View
  • 118 Download
  • 3 Citations
PDF
Clear Cell Papulosis: A Case Report
So-Woon Kim, Jin Roh, Chan-Sik Park
J Pathol Transl Med. 2016;50(5):401-403.   Published online May 29, 2016
DOI: https://doi.org/10.4132/jptm.2016.02.16
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  • 120 Download
  • 5 Citations
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JPTM : Journal of Pathology and Translational Medicine