Journal of Pathology and Translational Medicine

Original Article

Polo-like kinase 4 as a potential predictive biomarker of chemoradioresistance in locally advanced rectal cancer: Hyunseung Oh, Soon Gu Kim, Sung Uk Bae, Sang Jun Byun, Shin Kim, Jae-Ho Lee, Ilseon Hwang, Sun Young Kwon, Hye Won Lee; J Pathol Transl Med. 2022;56(1):40-47. Published online November 16, 2021; DOI: https://doi.org/10.4132/jptm.2021.10.07

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Abstract PDF Supplementary Material: Background
Polo-like kinase 4 (PLK4) is a serine/threonine protein kinase located in the centriole of the chromosome during the cell cycle. PLK4 overexpression has been described in a variety of many common human epithelial tumors. Conversely, PLK4 acts as a haploinsufficient tumor suppressor in some situations, highlighting the importance of strict regulation of PLK4 expression, activity, and function. Meanwhile, the importance of chemoradiation resistance in rectal cancer is being emphasized more than ever. We aimed to analyze PLK4 expression and the tumor regression grade (TRG) in patients with rectal cancer, treated with chemoradiotherapy (CRT).
Methods
A retrospective study was conducted on 102 patients with rectal cancer who received preoperative CRT. Immunohistochemistry for PLK4 in paraffin-embedded tissue was performed from the biopsy and surgical specimens.
Results
We found significant association between high expression of PLK4 and poor response to neoadjuvant CRT (according to both Mandard and The Korean Society of Pathologists TRG systems) in the pre-CRT specimens. Other clinicopathologic parameters did not reveal any correlation with PLK4 expression.
Conclusions
This study revealed an association between high expression of PLK4 in the pre-CRT specimens and TRG. Our results indicated that PLK4 could potentially be a new predictor for CRT effect in patients with rectal cancer.

Case Report

Ovarian Sertoli-Leydig Cell Tumors with Heterologous Gastrointestinal Type Epithelium or with Striated Skeletal Muscle: report of two cases.: Ki Ouk Min, Eun Joo Seo, Young Shin Kim, Kyo Young Lee, Sang In Shim; Korean J Pathol. 1996;30(1):50-56.

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Abstract PDF: Sertoli-Leydig cell tumors of the ovary are rare, accounting for no more than 0.5% of all ovarian neoplasms. These tumors occur predominantly in women 10 to 30 years of age. Heterologous elements are found in over 20% of the moderately and poorly differentiated Sertoli- Leydig cell tumors. The most common element is gastrointestinal mucin-secreting epithelium, found in approximately 20% of all cases. Approximately 4% of Sertoli-Leydig cell tumors contain immature skeletal muscle and/or cartilaginous elements. The origin of these neoplasms is regarded as neometaplasia of the mesodermal neoplastic element. While the degree of differentiation of Sertoli-Leydig cell tumors is probably of greater importance in determining prognosis than the presence of heterologous components, recent evidence does point to an unfavorable effect on clinical outcome when heterologous mesenchymal components such as cartilage and striated muscle are present. We experienced two cases of ovarian heterologous Sertoli-Leydig cell tumors with gastrointestinal type epithelium and striated skeletal muscle in 20 and 21 year-old females, respectively. One case involved a patient who had complained of amenorrhea for 3 years while the other case involved a patient who had complained of left lower abdominal tenderness and amenorrhea for one and one half years. It was determined by ultrasonography of the pelvis that the two patients suffered from right and left ovarian masses. Both patients underwent adnexectomy. These tumors were large with partly solid and partly cystic areas. Based on light microscopic examination one case was classified as an intermediate Sertoli-Leydig cell tumor with heterologous gastrointestinal type epithelium, while the other case was classified as a poorly differentiated Sertoli-Leydig cell tumor with heterologous striated skeletal muscle.

Original Article

Expression of p53 and nm23 Proteins in Non-Small Cell Lung Cancer.: Mi Seon Kwon, Won Il Kim, Kyo Young Lee, Young Shin Kim, Chang Suk Kang, Sang In Shim; Korean J Pathol. 1997;31(6):499-507.

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Abstract PDF: To elucidate the role of p53 and nm23 in the development, progression, and metastasis of non-small cell lung cancer, we studied 91 paraffin sections of the primary non-small-cell lung cancers and the 34 paraffin sections of their metastatic lymph nodes using the immunohistochemical method. The results are as follows: 1) The incidence of p53 protein expression was positively correlated with the staging of lung cancers (p<0.025). 2) The incidence of p53 protein expression was higher in the lung cancers with lymph node metastasis than in those without lymph node metastasis (p=0.009). 3) The incidence of nm23 protein expression was lower in the adenocacinomas than in the squamous cell carcinomas (p=0.032). 4) The incidence of nm23 protein expression was lower in the lung cancers with lymph node metastasis than in those without lymph node metastasis (p=0.026). The expression of nm23 protein between the primary lung cancers and corresponding metastatic lymph nodes showed positive correlation (Kendall's Tau-b correlation coefficient=0.47140, p=0.0068). 5) The expression of p53 was not correlated with the expression of nm23 protein (Kendall's Tau-b correlation coefficient=0.11387, p=0.2800). The above results suggest that an overexpression of p53 protein and a downregulation of nm23 protein are associated with tumor progression and metastasis in non-small-cell lung cancer.

Case Reports

Bilateral Elastofibroma: Report of a case.: Sung Chul Lim, Mi Sook Lee, You Kyung Jeong, Yun Shin Kim, Hyun Jong Park, Mi Ja Lee; Korean J Pathol. 1997;31(6):589-591.

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Abstract PDF: Elastofibroma is a rare benign tumor-like condition manifesting as firm and spherical mass with poorly circumscribed margins of fibroelastic tissue, occuring in the subscapular region or the chest wall of elderly persons. It is not a true neoplasm but rather a reactive or degenerative process causing abnormal elastogenesis. It is unilateral in the majority of cases and the right side is affected more commonly than the left. We report a case of bilateral elastofibromas removed from both subscapular regions of a 73-year-old female farmer. She was presented with tender masses on the bilateral subscapular areas for seven years. Microscopically, it consisted of a mixture of intertwining broad eosinophilic collagen bundles and elastic fibers associated with a few fibroblasts and mature fat cells. The elastic fibers had a degenerated beaded appearance or were fragmented into serrated globules in a linear arrangement.

Benign Cystic Mesothelioma.: Sung Chul Lim, You Kyung Jeong, Mi Sook Lee, Yun Shin Kim, Hyun Jong Park, Sang Joon Choi; Korean J Pathol. 1997;31(6):595-597.

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Abstract PDF: Benign cystic mesothelioma (BCM) is a rare mesothelial lesion that forms multicystic masses in the upper abdomen, pelvis and retroperitoneum. Although it is categorized as a benign lesion, it has a tendency to recur. It is uncertain whether the nature of this lesion is reactive or neoplastic, but many articles support the conclusion that it is reactive rather than neoplastic. The majority of cases were associated with a history of a previous abdominal or pelvic operation, or an evidence of endometriosis or a pelvic inflammatory disease, or a combination of these findings. In a 26-year-old woman we experienced a case of BCM which was incidentally discovered at cesarean delivery revealing multilocular thin and translucent walled cysts in the pelvic cavity. Microscopic examination revealed a thin cyst wall that was composed of fibrous connective tissue and lined by internal stratified and external nonstratified single cuboidal epithelia.

Mucous Gland Adenoma of the Bronchus; Light Microscopic and Ultrastructural Features.: Mi Seon Kwon, Kyo Young Lee, Young Shin Kim, Chang Suk Kang, Sang In Shim; Korean J Pathol. 1997;31(9):898-901.

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Abstract PDF: We present a case of mucous gland adenoma arising from the main bronchus of the lower lobe of the left lung in terms of clinicopathologic, immunohistochemical, and ultrastructural aspects as well as review of related literatures. The patient, a 31-year-old female, was admitted to Catholic University Medical College Hospital with complaints of coughing and purulent sputum for about seven years. The chest CT showed a severely calcified tumor in the left lower lobe of the lung. Grossly, the calcified tumor arising from the main bronchus protruded into the lumen and showed bronchiectasis of the lower lobe and atelectasis of the upper lobe of the lung. The tumor was pale brown-gray and sharply circumscribed and showed some small cystic spaces filled with mucoid material. Microscopically, most of the tumor showed dystrophic calcification. The growth pattern of the tumor is composed of cysts, tubules, and glands lined by cytologically bland columnar, cuboidal, or flattened mucus secreting cells. Electron micrograph of tumor cells showed some round or oval mucous granules measuring 0.5-1.8 micrometer.

Original Article

Expression of the nm23 and E-cadherin Proteins in Breast Carcinoma.: Jean a Kim, Won Il Kim, Sang In Shim, Chang Suck Kang, Kyo Young Lee, Young Shin Kim; Korean J Pathol. 1998;32(1):29-34.

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Abstract PDF: Expression of the nm23 and E-cadherin proteins has been studied in a number of tumors. Reduced expression of the nm23 and E-cadherin proteins seems to be associated with metastasis or disease progression in some tumors, including breast carcinoma. To assess the role of nm23 and E-cadherin in tumor differentiation and metastasis of breast carcinoma, immunohistochemical staining for the nm23 and E-cadherin proteins was performed in paraffin embedded tumor samples from 86 breast carcinomas. The results were as follows: 1) Expression of the nm23 protein in breast carcinoma was strong positive in 32 cases (37.2%), weak positive in 26 cases (30.2%), and negative in 28 cases (32.6%) of the cases. Expression of the nm23 protein in breast carcinoma decreased according to histological grade and lymph node metastasis, but was not statistically significant. 2) Expression of the E-cadherin protein in breast carcinoma was strong positive in 50 cases (58.1%), weak positive in 24 cases (27.9%), and negative in 12 cases (14%) of the cases. Expression of the E-cadherin protein in breast carcinoma decreased according to histological grade and lymph node metastasis, but was not statistically significant. 3) There was a statistically significant correlation between the expression of the nm23 protein and the E-cadherin protein in breast carcinoma (p<0.05). These results suggest that the expression of the nm23 and E-cadherin proteins is related to tumor differentiation, and may also be an useful prognostic factor in breast carcinoma.

Case Report

Pulmonary Pseudallescheriasis: A case report and Histopathologic Comparision with Pulmonary Aspergillosis.: Young Sill Kim, Chang Suk Kang, Kyung Ja Han, Kyo Young Lee, Sang In Shim, Young Shin Kim; Korean J Pathol. 1998;32(2):147-149.

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Abstract PDF: Infection by pseudallescheria boydii is an occasional cause of mycetoma, corneal ulcers, endophthalitis, sinusitis, pneumonia, endocarditis, meningitis, arthritis, and osteomyelitis. But, it also causes serious disseminated or localized infection in immunocompromised patients. We report a case of pulmonary pseudallescheriasis developed in a 32-year-old man who has been a sofa manufacturer for several years. He presented with a cystic mass in the lung, 5cm in the largest dimension. Dark green necrotic material was evacuated from the cavity. Microscopically, the cystic wall and adjacent lung parenchyme were infiltrated by histiocytes rather than eosinophils and there was little fibrosis in the wall. The P. boydii was isolated from the cystic contents, which revealed white floccose colonies in Sabouraud dextrose agar and revealed single or multiple-celled oval conidia being produced on short hyalinated hyphae and on the elongated annellides in the slide culture. The differential findings with aspergillosis are discussed.

Original Articles

Immunohistochemical Study of p53 and E-cadherin Proteins in Prostate Carcinoma.: Lee So Maeng, Won Il Kim, Kyo Young Lee, Young Shin Kim, Chang Suk Kang, Sang In Shim; Korean J Pathol. 1998;32(3):215-221.

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Abstract PDF: Considerable controversy exists concerning the value of histomorphological data in the assessment of the malignant potential of prostate carcinomas. Mutations in the p53 gene resulting in the accumulation of altered p53 proteins with prolonged half-life have been found in a large variety of human malignancies. E-Cadherin is a specific epithelial cell-to- cell adhesion molecule which has previously been found to be expressed in well-differentiated non-invasive carcinoma cell lines, but it is lost in many poorly differentiated invasive cell lines. We performed immunohistochemical staining of p53 and E-cadherin in formalin fixed paraffin embedded tissues of 58 primary prostatic carcinomas. The expression rates of p53 and E-cadherin proteins in prostate carcinoma were positive in 15.5% and 44.8% of the cases, respectively. Histologically high-grade prostate carcinoma shows an increased expression of the p53 protein and a decreased one of the E-cadherin protein (P<0.05). The expression rates of the E-cadherin protein in prostate carcinoma decreased significantly according to the higher clinical stages and PSA levels (P<0.05). There was no accordance between the expression rate of p53 and E-cadherin. There were no significant correlation between each of the clinical stages and the expression rate of p53 protein or the PSA levels and the expression rates of p53 protein (P<0.05). Based on the present study, the expression of p53 and down regulation of E-cadherin are correlated with tumor progression and metastasis, and may be a useful prognostic factor in prostate carcinoma.

Detection of Minimal Lesion and Identification of Clonality in Malignant Lymphoma.: Young Shin Kim, Chang Suk Kang, Kyun gja Han, Kyo Young Lee, Yong Goo Kim, Won Il Kim, Sang In Shim; Korean J Pathol. 1998;32(4):298-308.

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Abstract PDF: The bone marrow biopsy is an integral part of the staging process in patients with malignant lymphomas. Bone marrow(BM) involvement indicates stage IV disease, but there are always a lot of cases in which clear separation is not possible when based on morphology alone. Additional difficulties are caused by morphologic discordance between the BM and the primary lymphoma. Immunohistochemical stain, mRNA in situ hybridization (ISH) for light chain restriction and polymerase chain reaction (PCR) for IgH CDR3 and TCRgamma were performed to find a minimal lesion and the clonality in formalin fixed paraffin embedded tissues of 39 primary lymphomas and corresponding BM biopsy specimens. As a result, nine morphologically negative bone marrows of 18 lymphomas were positive by PCR (Group I). Among the 6 lymphoma cases with morphologically suspicious BM involvement (Group II), one was confirmed to be positive for marrow involvement by both mRNA ISH and PCR and the other four by PCR alone. The positive bone marrows of Group I and II revealed gene rearrangement at the same site as the primary lesion, suggesting the same clonality. Thirteen of 15 lymphomas with morphologically positive BM (Group III) had the same clonality in the primary lymphomas and the BM lesion. Three cases among the Group III with morphologic discordance also revealed the same clonality by PCR. This study shows that a combination of mRNA ISH and PCR in addition to an immunohistochemical stain improves the diagnostic sensitivity in the detection of BM involvement and identification of clonality. Among the three different methods used, PCR is the most sensitive in detecting a minimal lesion.

Paneth Cell-rich Carcinoma of the Stomach: A case report .: Ah Won Lee, Young Shin Kim, Kyo Young Lee, Chang Suk Kang, Sang In Shim; Korean J Pathol. 1998;32(8):613-615.

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Abstract: Paneth cell-rich carcinoma is essentially an adenocarcinoma with a predominance of Paneth cells. A 60-year-old male patient was admitted with a history of abdominal distension for several months. Endoscopic examination revealed a large ulceroinfiltrative tumor involving most of the areas of the stomach. The biopsy of the lesion confirmed poorly differentiated adenocarcinoma and total gastrectomy was followed. The submitted total stomach contained a diffuse infiltrative Borrmann type IV mass with ulceration, 8.0 3.5 cm, at the body along the lesser curvature. Microscopically, it was composed of Paneth cell differentiated cancer cells and poorly differentiated tubular adenocarcinoma cells. The Paneth cell differentiation was characterized by cytoplasmic coarse eosinophilic granules, which were PAS-positive and positive reaction for lysozyme. Electron microscopic examination showed numerous, spherical, electron-dense, homogeneous granules corresponding to those in Paneth cells as well as mucin granules in the signet-ring cells, and various intermediate forms in some cancer cells, which might be immature in the Paneth cell lineage.

Case Reports

Serratia marcescens Skin Abscess.: Chan Kwon Jung, Young Shin Kim, Kyo Young Lee, Kyungja Han, Chang Suk Kang, Sang In Shim, Jun Young Lee, Baik Kee Cho; Korean J Pathol. 1998;32(11):1032-1034.

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Abstract: Serratia marcescens is the most important member of the genus Serratia and causes opportunistic infections, particularly pneumonia and septicemia in patients with malignancy, renal failure (acute and chronic), and diabetes mellitus. The most common portals of entry are known to be, in descending order, lung, genitourinary tract, intravenous line, gastrointestinal tract, and skin. S. marcescens rarely causes skin infection because it does not normally colonize human skin. Only six cases of S. marcescens cellulitis were reported. Five of them were immunocompromised patients. We have experienced a case of skin abscess caused by S. marcescens, which was found in a 59-year-old woman. She was undergoing prior antibiotic treatment after insulinoma surgery. S. marcescens was isolated from the skin abscess as a sole organism. She was treated with appropriate antibiotics that exhibited sensitivities for the organism and cured without any complication. The authors report a case of S. marcescens infection on the skin of a 59-year-old woman and review the literature concerning this organism as a causative agent.

Heterotopic Brain Tissue in the Soft Palate.: Hyun Joo Choi, Youn Soo Lee, Young Shin Kim, Kyo Young Kim, Chang Suk Kang, Sang In Shim; Korean J Pathol. 1998;32(11):1039-1041.

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Abstract: Heterotopic brain tissue is a developmental anomaly of neurogenic origin with no malignant potential, and is usually present around the nose of children and infants. So it has been called nasal glioma. But, even more rarely, heterotopic glial tissue may be found in various sites other than nasal cavity, such as the ethmoidal sinus, palate, tonsillar area, pharynx, ear, subcutaneous tissue, lung, and female genital tract. We experienced a more unusual case of a polypoid heterotopic brain tissue in the soft palate in a 3-year-old boy. The mass was microscopically reminiscent of "gliosis" of the central nervous system and interestingly contained choroid plexus focally. The glial nature of the lesion was confirmed by glial fibrillary acidic protein immunostain.

Original Articles

The Expression of p53, c-erbB-2 and nm23 Proteins in Breast Cancer.: Kyo Young Lee, Yong Goo Kim, Young Shin Kim, Kyung Ja Han, Chang Suk Kang, Jean A Kim, Won Il Kim, Sang In Shim; Korean J Pathol. 1999;33(2):88-95.

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Abstract: Recently, p53, c-erbB-2 and nm23 proteins have been studied in breast cancer. The expression of p53 protein indicates the mutation of p53 gene known as a tumor supressor gene, and c-erbB-2 gene amplification has been considered an indicator of poor prognosis and nm23 a metastsis suppressor gene. In order to elucidate the roles and relations of these proteins in the develpoment, progression and metastasis in breast cancer, we studied 89 cases of invasive breast cancer and 32 cases of lymph node metastasis for the expression of p53, c-erbB-2 and nm23 proteins using an immunohistochemical method. The results were as follows: 1) The expression rates of p53, c-erbB-2, and nm23 proteins in breast cancer were 40.4%, 34.8% and 55.1%, respectively. Co-expression of p53 protein and c-erbB-2 protein was found in 20.2% of cases, showing the highest incidence in poorly differentiated type (40%). 2) p53 protein expression was increased in poorly differentiated type but was not statistically significant. On the other hand, the expression of nm23 protein was decreased in poorly differentiated type, which was statistically significant (p<0.05). 3) The correlation of p53 protein expression with c-erbB-2 protein expression was statistically significant (p<0.05) but that with nm23 protein was not. 4) In the cases with lymph node metastasis, discordant expression of p53, c-erbB-2 and nm23 proteins between primary tumor and the lymph node metastatic tumor was found in 9.4%, 3.1% and 18.8% of cases, respectively. The above results suggest that overexpression of p53 and c-erbB-2 proteins and downregulation of nm23 protein are associated with the tumor progression in the breast cancer.

Loss of Heterozygosity of Chromosome 3p in Squamous Cell Carcinomas and Adenocarcinomas of the Lung.: Gyeong Shin Park, Young Shin Kim, Kyo Young Lee, Chang Suk Kang, Sang In Shim, Byung Kee Kim; Korean J Pathol. 1999;33(3):151-157.

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Abstract PDF: We evaluated the frequency of genetic alteration of chromosome 3p in lung cancer, and analyzed the patterns of genetic alterations between two distinct histologic types, squamous cell carcinomas (SCC) and adenocarcinomas (AC). PCR-LOH analysis for 40 Korean non-small cell lung cancer including 20 SCC and 20 AC was performed using microsatellite markers, D3S1300, D3S1029 and D3S1038. These markers represented the loci of FHIT gene (3p14), mismatch repair gene hMLH1 (3p21) and VHL gene (3p25), respectively. For SCC, the frequency of LOH at D3S1300, D3S1029 and D3S1038 was 78.6%, 61.5% and 64.3%, and for AC, was 62.5%, 62.5% and 46.7%, and for total 40 cases of SCC and AC, was 70.0%, 62.1% and 55.2%, respectively. Among 27 cases showing heterozygosity at three examined loci, 7 cases (25.9%) revealed LOH at only one locus and 16 cases (59.3%) revealed LOH at two or three loci. The differences of incidence of LOH and the patterns of genetic alterations at chromosome 3p between two distinct histologic types of lung cancer were not significant. The genetic deletion of relatively broad area, including more than two loci, was more frequent than that of small area, including only one locus.

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