Journal of Pathology and Translational Medicine

Original Articles

The combination of CDX2 expression status and tumor-infiltrating lymphocyte density as a prognostic factor in adjuvant FOLFOX-treated patients with stage III colorectal cancers: Ji-Ae Lee, Hye Eun Park, Hye-Yeong Jin, Lingyan Jin, Seung Yeon Yoo, Nam-Yun Cho, Jeong Mo Bae, Jung Ho Kim, Gyeong Hoon Kang; Received June 3, 2024 Accepted September 26, 2024 Published online October 24, 2024; DOI: https://doi.org/10.4132/jptm.2024.09.26 [Epub ahead of print]

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Abstract PDF Supplementary Material: Background
Colorectal carcinomas (CRCs) with caudal-type homeobox 2 (CDX2) loss are recognized to pursue an aggressive behavior but tend to be accompanied by a high density of tumor-infiltrating lymphocytes (TILs). However, little is known about whether there is an interplay between CDX2 loss and TIL density in the survival of patients with CRC.
Methods
Stage III CRC tissues were assessed for CDX2 loss using immunohistochemistry and analyzed for their densities of CD8 TILs in both intraepithelial (iTILs) and stromal areas using a machine learning-based analytic method.
Results
CDX2 loss was significantly associated with a higher density of CD8 TILs in both intraepithelial and stromal areas. Both CDX2 loss and a high CD8 iTIL density were found to be prognostic parameters and showed hazard ratios of 2.314 (1.050–5.100) and 0.378 (0.175–0.817), respectively, for cancer-specific survival. A subset of CRCs with retained CDX2 expression and a high density of CD8 iTILs showed the best clinical outcome (hazard ratio of 0.138 [0.023–0.826]), whereas a subset with CDX2 loss and a high density of CD8 iTILs exhibited the worst clinical outcome (15.781 [3.939–63.230]).
Conclusions
Altogether, a high density of CD8 iTILs did not make a difference in the survival of patients with CRC with CDX2 loss. The combination of CDX2 expression and intraepithelial CD8 TIL density was an independent prognostic marker in adjuvant chemotherapy-treated patients with stage III CRC.

Loss of Human Leukocyte Antigen Class I Expression Is Associated with Poor Prognosis in Patients with Advanced Breast Cancer: Hong Sik Park, Uiju Cho, So Young Im, Chang Young Yoo, Ji Han Jung, Young Jin Suh, Hyun Joo Choi; J Pathol Transl Med. 2019;53(2):75-85. Published online November 14, 2018; DOI: https://doi.org/10.4132/jptm.2018.10.11

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Background
Human leukocyte antigen class I (HLA-I) molecules play important roles in regulating immune responses. Loss or reduction of HLA-I expression has been shown to be associated with prognosis in several cancers. Regulatory T-cells (Tregs) also play critical functions in immune response regulation. Evaluation of HLA-I expression status by the EMR8-5 antibody and its clinical impact in breast cancer have not been well studied, and its relationship with Tregs remains unclear.
Methods
We evaluated HLA-I expression and Treg infiltration by immunohistochemistry in 465 surgically resected breast cancer samples. We examined the correlation between HLA-I expression and Treg infiltration and clinicopathologic characteristics and survival analyses were performed.
Results
Total loss of HLA-I expression was found in 84 breast cancer samples (18.1%). Univariate survival analysis revealed that loss of HLA-I expression was significantly associated with worse disease-specific survival (DSS) (p = .029). HLA-I was not an independent prognostic factor in the entire patient group, but it was an adverse independent prognostic factor for DSS in patients with advanced disease (stage II–IV) (p = .031). Treg numbers were significantly higher in the intratumoral stroma of HLA-I–positive tumors than in HLA-I–negative tumors (median 6.3 cells/high power field vs 2.1 cells/high power field, p < .001). However, Tregs were not an independent prognostic factor in our cohort.
Conclusions
Our findings suggest that the loss of HLA-I expression is associated with poor prognosis in breast cancer patients, highlighting the role of HLA-I alterations in immune evasion mechanisms of breast cancer. HLA-I could be a promising marker that enables the application of more effective and precise immunotherapies for patients with advanced breast cancer.

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CD9 Expression in Colorectal Carcinomas and Its Prognostic Significance: Kyung-Ju Kim, Hee Jung Kwon, Min Chong Kim, Young Kyung Bae; J Pathol Transl Med. 2016;50(6):459-468. Published online October 25, 2016; DOI: https://doi.org/10.4132/jptm.2016.10.02

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Abstract PDF

Background
CD9, a member of the tetraspanin superfamily, is a tumor suppressor in many malignancies. The aim of this study was to evaluate the immunohistochemical expression of CD9 in colorectal carcinomas (CRCs) and determine clinicopathological and prognostic significance of its expression.
Methods
The CD9 expression status of 305 CRCs was evaluated using a semi-quantitative scoring system in tumor cells (T-CD9) and immune cells (I-CD9) by classifying the results as high and low expression.
Results
High T-CD9 (T-CD9 [+]) expression was detected in 175 samples (57.6%) and high I-CD9 (I-CD9 [+]) expression was detected in 265 samples (86.9%). Using Kaplan- Meier survival analysis, the T-CD9 (+) group showed a tendency for better disease-free survival (DFS) (p = .057). In left-sided tumors, DFS was significantly longer in the T-CD9 (+) group (p = .021) but no statistical significance was observed with right-sided tumors (p = .453). I-CD9 (+) CRCs significantly correlated with well/moderately differentiation (p = .014). In Kaplan-Meier analysis, the I-CD9 (+) group had a tendency towards worse DFS compared to the I-CD9 (–) group (p = .156). In combined survival analysis of T-CD9 and I-CD9, we found that the longest DFS was among patients in the T-CD9 (+)/I-CD9 (–) group, whereas the T-CD9 (–)/I-CD9 (+) group showed the shortest DFS (p = .054).
Conclusions
High expression of T-CD9 was associated with a favorable DFS, especially in left-sided CRCs. Combined evaluation of T-CD9 and I-CD9 is required to determine the comprehensive prognostic effect of CD9 in CRCs.

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Proteomic analysis of plasma exosomes in patients with metastatic colorectal cancer
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Proteomic Signature of Extracellular Vesicles Associated with Colorectal Cancer
Natalia Soloveva, Svetlana Novikova, Tatiana Farafonova, Olga Tikhonova, Victor Zgoda
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Nuclear Expression of Hepatitis B Virus X Protein Is Associated with Recurrence of Early-Stage Hepatocellular Carcinomas: Role of Viral Protein in Tumor Recurrence: Jing Jin, Hae Yoen Jung, KyuHo Lee, Nam-Joon Yi, Kyung-Suk Suh, Ja-June Jang, Kyoung-Bun Lee; J Pathol Transl Med. 2016;50(3):181-189. Published online April 17, 2016; DOI: https://doi.org/10.4132/jptm.2016.03.18

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Abstract PDF

Background
Hepatitis B virus (HBV) plays well-known roles in tumorigenesis of hepatocellular carcinoma (HCC) in infected patients. However, HBV-associated protein status in tumor tissues and the relevance to tumor behavior has not been reported. Our study aimed to examine the expression of HBV-associated proteins in HCC and adjacent nontumorous tissue and their clinicopathologic implication in HCC patients.
Methods
HBV surface antigen (HBsAg), HBV core antigen (HBcAg), and HBV X protein (HBx) were assessed in 328 HBV-associated HCCs and in 155 matched nontumorous tissues by immunohistochemistry staining.
Results
The positive rates of HBsAg and cytoplasmic HBx staining in tumor tissue were lower than those in nontumorous tissue (7.3% vs. 57.4%, p < .001; 43.4% vs. 81.3%, p < .001). Conversely, nuclear HBx was detected more frequently in tumors than in nontumorous tissue (52.1% vs. 30.3%, p < .001). HCCs expressing HBsAg, HBcAg, or cytoplasmic HBx had smaller size; lower Edmondson-Steiner (ES) nuclear grade, pT stage, and serum alpha-fetoprotein, and less angioinvasion than HCCs not expressing HBV-associated proteins. Exceptionally, nuclear HBx-positive HCCs showed higher ES nuclear grade and more frequent large-vessel invasion than did nuclear HBx-negative HCCs. In survival analysis, only nuclear HBx-positive HCCs had shorter disease-free survival than nuclear HBx-negative HCCs in pT1 and ES nuclear grade 1–2 HCC subgroup (median, 126 months vs. 35 months; p = .015).
Conclusions
Our data confirmed that expression of normal HBV-associated proteins generally decreases in tumor cells in comparison to nontumorous hepatocytes, with the exception of nuclear HBx, which suggests that nuclear HBx plays a role in recurrence of well-differentiated and early-stage HCCs.

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The Expression of CD10 and CD15 Is Progressively Increased during Colorectal Cancer Development: Tae Jung Jang, Jeong Bae Park, Jong Im Lee; Korean J Pathol. 2013;47(4):340-347. Published online August 26, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.4.340

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Abstract PDF

Background

The aim of this study was to examine the expression of CD10 and CD15 in tumor cells, stromal cells and infiltrating inflammatory cells during colorectal carcinoma (CRC) development and to investigate their expression levels between the tumor center and invasive front and compare them to clinicopathological parameters in invasive CRC.

Methods

We performed immunohistochemical staining for CD10, CD15, and E-cadherin in 42 cases of CRC, 49 of tubular adenoma, 15 of hyperplastic polyp, and 17 of non-neoplastic colon.

Results

CD10 was expressed in tumor cells (tCD10), stromal cells (sCD10) and infiltrating inflammatory cells (iCD10), and CD15 was expressed in tumor cells (tCD15) and infiltrating inflammatory cells (iCD15). Their expressions were progressively increased during CRC development and the iCD10 expression level was significantly correlated with the iCD15 expression level in invasive CRC. Invasive front revealed a higher expression level of iCD10 and iCD15 than the tumor center. Moreover, the iCD15 expression level of invasive front was significantly correlated with the degree of tumor budding and tCD15 in whole tissue sections was closely associated with tumor depth.

Conclusions

The present study suggests that the expression of CD10 and CD15 is associated with the development and progression of CRC.

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Case Reports

Solitary Fibrous Tumor of the Conjunctiva with Heretofore Undescribed Pathologic Findings.: Na Rae Kim, Jae Y Ro, Kyung Hwan Shin, Hae Jung Paik, Jung Suk An, Seung Yeon Ha; Korean J Pathol. 2011;45(3):315-318.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.3.315

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Abstract PDF

A 37-year-old female presented with a conjunctival mass discovered 3 years prior. An excisional biopsy revealed a patternless proliferation of round and spindle-shaped cells with an eosinophilic fibrillary cytoplasm and vesicular nuclei with occasional inclusions. Psammoma bodies were arranged around the dilated irregularly-shaped vessels. Differential diagnoses included conjunctival solitary fibrous tumor (SFT), nevus, glomangioma, ectopic meningioma, and mesectodermal leiomyoma. The tumor cells were immunoreactive for CD34, CD99, bcl-2 and vimentin, and were negative for smooth muscle actin, desmin, glial fibrillary acidic protein, S-100 protein, epithelial membrane antigen, and human melanoma black-45. Ultrastructurally, the tumor cells had rough endoplasmic reticulum, free ribosomes, and scattered mitochondria without basal lamina or cellular junctions, which are features of fibroblasts. A diagnosis of SFT was rendered based on the light microscopic, immunohistochemical, and electron microscopic findings. We report here on the second case of a SFT arising in the conjunctiva, which clinically and histologically mimics conjunctival nevus, glomangioma, ectopic meningioma, and a hybrid neurogenic-myogenic tumor such as mesectodermal leiomyoma.

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Meningeal Solitary Fibrous Tumors with Delayed Extracranial Metastasis
Nayoung Han, Hannah Kim, Soo Kee Min, Sun-Ha Paek, Chul-Kee Park, Seung-Hong Choi, U-Ri Chae, Sung-Hye Park
Journal of Pathology and Translational Medicine.2016; 50(2): 113. CrossRef

Sclerosing Angiomatoid Nodular Transformation (SANT) in Spleen: A Case Report.: Hyun Jung Lee, Song Yi Choi, Song Mei Huang, Ji Young Sul, Jin Man Kim; Korean J Pathol. 2011;45(1):111-114.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.1.111

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Abstract PDF

Sclerosing angiomatoid nodular transformation (SANT) of spleen is a rare inflammatory tumor-like vascular lesion composed of angiomatoid nodules in a fibrosclerotic background. We report herein on a case of SANT in the spleen with its pathologic features, and review the related literature. A 50-year-old woman presented with mild left upper quadrant discomfort and tenderness and she showed a 6 cm-sized solitary splenic mass on computed tomography. She underwent laparoscopic splenectomy. Grossly, the spleen showed a well circumscribed round-shaped solid mass with multinodular hemorrhagic surfaces. Microscopically, the mass consisted of multiple angiomatoid nodules surrounded by collagen bundles with fibroblasts and a lymphoplasma cell infiltration. Immunohistochemically, the cells of the angiomatoid nodules were positive for CD31, CD30, CD34, alpha-smooth muscle actin, and VWF-VIII, but they were negative for CD8, anaplastic lymphoma kinase protein, and D2-40. The patient has been under close follow-up without recurrence.

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Sclerosing angiomatoid nodular transformation of the spleen presenting rapid growth after adrenalectomy: Report of a case
Yasuo Nagai, Daisuke Satoh, Hiroyoshi Matsukawa, Shigehiro Shiozaki
International Journal of Surgery Case Reports.2017; 30: 108. CrossRef
A Case of Sclerosing Angiomatoid Nodular Transformation of the Spleen: Spoke Wheel Pattern on Computed Tomography
Joo Han Park, Sun Hyuk Hwang, Ki Chan Kim, Si Yeon Kim, Ga Won Song, Jae Ho Han, Joon Seong Park
Korean Journal of Medicine.2014; 86(3): 357. CrossRef
Differentiation of an Unclear Splenic Lesion in a Patient With Cholangiocarcinoma
Constantin Lapa, Ulrich Steger, Christian O. Ritter, Vanessa Wild, Ken Herrmann
Clinical Nuclear Medicine.2014; 39(5): 470. CrossRef
Sclerosing Angiomatoid Nodular Transformation of the Spleen: CT and MRI Features With Pathologic Correlation
Rachel B. Lewis, Grant E. Lattin, Meenakshi Nandedkar, Nadine S. Aguilera
American Journal of Roentgenology.2013; 200(4): W353. CrossRef

Original Articles

CD44 and MMP14 Expression Associated with WHO Grade of the Astrocytoma and the Prognostic Implications.: Jaekyung Myung, Bogun Jang, Heae Surng Park, Woongjae Yon, Hyun Ju Lee, Sung Hye Park; Korean J Pathol. 2010;44(1):35-41.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.1.35

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Abstract PDF: BACKGROUND
CD44 is a cell surface receptor that has been implicated in tumor cell invasion and metastasis in a range of tumors of various organs, including breast, ovary, colon, lung, and brain. CD44 stimulates the invasive ability by interacting with matrix metalloproteinase 14 (MMP14). The expression of MMP14 on the cell surface is thought to trigger multiple proteinase cascades and to stimulate cell migration.
METHODS
A total 54 astrocytoma patients were eligible for this study. We performed a retrospective clinicopathological review and CD44 and MMP14 immunohistochemistry.
RESULTS
The expressions of CD44 and MMP14 were significantly correlated with the World Health Organization (WHO) grade. On univariate analysis, the WHO grade and the expression of CD44 were the significant prognostic factors affecting overall survival (OS) and disease progression free survival (DPFS). On the multivariate analysis by the Cox regression model, the only WHO grade was shown to be a significant independent prognostic factor for predicting the DPFS and OS.
CONCLUSIONS
In this study, the CD44 and MMP14 expressions were related to the WHO grade of astrocytoma. The CD44 expression status was a prognostic factor for DPFS and OS on univariate analysis, but it was not an independent prognostic factor on the multivariate analysis.

Detection of SV40 Large T Antigen in Malignant Lymphomas.: Young A Kim, MeeSoo Chang, Jinho Paik, Sun Och Yoon, Yoon Kyung Jeon, Chul Woo Kim, Ji Eun Kim; Korean J Pathol. 2009;43(4):312-316.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.4.312

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Abstract PDF

BACKGROUND
The association of simian virus 40 (SV40) with certain types of human cancers, including malignant lymphomas, has been a topic of interest for some time. Although the virus is distributed worldwide, its incidences vary according to the specific types of tumors, and the epidemiological areas. The aim of this study was to investigate the frequency of SV40 in malignant lymphomas among Korean patients. METHODS: One hundred seventy three cases of malignant lymphomas were evaluated by immunohistochemical staining for SV40 large T antigen (TAg), using an extremely sensitive, tyramide based, catalyzed signal amplification method. RESULTS: From 158 non-Hodgkin's lymphomas, including 115 diffuse large B-cell lymphomas, and 15 Hodgkin's lymphomas, none of the cases were positive for SV40 TAg. CONCLUSIONS: SV40 does not appear to be related to the pathogenesis of malignant lymphomas among Koreans.

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No Detection of Simian Virus 40 in Malignant Mesothelioma in Korea
Minseob Eom, Jamshid Abdul-Ghafar, Sun-Mi Park, Joung Ho Han, Soon Won Hong, Kun Young Kwon, Eun Suk Ko, Lucia Kim, Wan Seop Kim, Seung Yeon Ha, Kyo Young Lee, Chang Hun Lee, Hye Kyoung Yoon, Yoo Duk Choi, Myoung Ja Chung, Soon-Hee Jung
Korean Journal of Pathology.2013; 47(2): 124. CrossRef

Expression of Fas/Fas Ligand and Its Relationship with Apoptosis in Chemically Induced Preneoplastic Lesions in Rat Liver.: Hye Jin Lee, Do Youn Park, Kyung Un Choi, Jee Yeon Kim, Chang Hun Lee, Mee Young Sol, Kang Suek Suh; Korean J Pathol. 2001;35(5):383-390.

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Abstract PDF: BACKGROUND
Apoptosis of hepatocytes plays a major role in experimental hepatocarcinogenesis of rats. But sequential change and localization of Fas and Fas ligand (FasL) in preneoplastic lesions and the relationship with apoptosis are not clearly elucidated.
METHODS
We investigated sequential change and localization of Fas/FasL and its relationship to apoptosis in preneoplastic lesions of chemical hepatocarcinogenesis in rats using northern blot analysis, immunohistochemistry and terminal deoxynucleotidyl transferase end labeling (TUNEL) assay.
RESULTS
We found that mRNA of Fas and Fas ligand increased for up to 42 days and 14 days after partial hepatectomy, respectively, and thereafter decreased with time. Fas protein was localized on the cytoplasm of hepatocytes of preneoplastic lesions, as well as on the cytoplasmic membrane of the adjacent liver parenchyme. Fas negative preneoplastic lesions were evident at 42 days after partial hepatectomy. FasL protein was found only in the cytoplasm of hepatocytes of preneoplastic lesions, instead of in the adjacent liver parenchyme. FasL-positive hepatocytes increased with time for up to 14 days after partial hepatectomy and therafter decreased. Also, TUNEL-positive apoptotic cells increased with time and were more numerous in the adjacent liver parenchyme than in the preneoplastic lesions.
CONCLUSIONS
It was suggested that Fas/FasL-mediated apoptosis might be one of the major mechanisms for controlling apoptotic cell death in the promotion stage of chemical hepatocarcinogenesis.

Case Report

Dendritic Myxofibrolipoma.: Sung Nam Kim, Kye Hyun Kwon, Yeon Lim Suh; Korean J Pathol. 2001;35(5):447-450.

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Abstract PDF: Dendritic myxofibrolipoma is a recently described disease entity that represents a distinctive benign soft tissue neoplasm showing the combined features of spindle cell lipoma and the solitary fibrous tumor. Immunohistochemical stains reveal a strong positivity for vimentin, CD34 and bcl-2, which highlight the dendritic nature of the tumor cells by demonstrating slender complex cytoplasmic prolongations. There have been 12 cases of dendritic myxofibrolipomas reported in literature. In Korea, none of the cases have been described. We report such a case with a 28-year-old man who had a palpable subcutaneous mass on his right shoulder for 4 months. Grossly, the removed mass measured 11X7X5 cm and appeared to be a well-encapsulated, lipomatous tumor with marked myxoid appearance. Microscopically, this tumor consisted of spindle cells admixed with dense collagen fibers and mature adipocytes in abundant myxoid stroma with high vascularity. Immunohistochemically, the tumor cells were strongly reactive for vimentin and CD34 and weakly reactive for bcl-2, and negative for S-100 protein.

Original Articles

Expressions of CD44s Is Associated with the Expression of Cyclooxygenase-2 in Non-Small Cell Lung Cancers.: Sung Jig Lim, Hyun Jung Kim, Jung Yeon Kim, Kyeongmee Park; Korean J Pathol. 2006;40(1):17-23.

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Abstract PDF: BACKGROUND
The overexpression of Cox-2 in tumors is important for tumor invasion, angiogenesis, resistance to apoptosis and the suppression of host immunity. Moreover, a tumor's CD44 expression plays an important role in tumor invasion and metastasis. We examined the expression of COX-2 and also CD44 and its variants as well as the biological implications and relationship between Cox-2 and the CD44 variants in non-small cell lung carcinoma.
METHODS
The expressions of Cox-2 and also CD44s and its variants (CD44v3 and CD44v6) were examined by performing immunohistochemistry on 98 surgical specimens.
RESULTS
The expressions of CD44s, CD44v3 and CD44v6 were significantly more frequent in squamous cell carcinoma specimens than in the adenocarcinoma (CD44s, p=0.033; CD44v3, p=0.007; CD44v6, p=0.022). The loss of CD44s and CD44v3 were significantly correlated with poor tumor differentiation (CD44s, p=0.03; CD44v3, p=0.011). Patients with Cox-2 positive-adenocarcinoma tumors had a significantly worse cumulative survival than did those adenocarcinoma patients without the Cox-2 (p=0.048). The expression of Cox-2 was significantly associated with the CD44s expression in non-small cell lung cancer, and especially in squamous cell carcinoma.
CONCLUSIONS
These findings suggest that expression of CD44s is associated with the expression of Cox-2 in NSCLC, and especially squamous cell carcinoma.

Expression of CD44 Isoforms and Its Significance in Renal Cell Carcinoma.: Ghil Suk Yoon, Hee Yeon Hong, Tae Sook Kim; Korean J Pathol. 2005;39(4):251-257.

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Abstract PDF: Background
: CD44 is a transmembranous glycoprotein that participates in cell-cell and cell-matrix interactions, and it also contributes to cell migration. In vitro studies have suggested that the expression of CD44 isoforms is associated with tumor metastasis. Since it is not clear whether the CD44 isoforms play a role in the tumorigenesis, differentiation, progression or metastasis of renal cell carcinomas (RCCs). Methods : We performed immunohistochemistry with primary antibodies for the standard CD44 (CD44s) and the CD44 variant exon 6 (CD44v6) on the archival paraffin-embedded tissue microarray (TMA) specimens from 51 RCC patients. Results : In the normal kidney, the expressions of both CD44s and CD44v6 were negligible. The CD44s expression was increased in accordance with the tumor size (p<0.01), but it was not related to the microvessel density (MVD). No CD44v6 expression was observed in all RCC cases. Univariate analysis indicated that stage, tumor size, lymph node metastasis and distant organ metastasis were the statistically significant prognostic factors for disease free survival (DFS) (p<0.01), and the multivariate analysis proved that stage (p<0.01) and tumor size (p<0.05) were the independent prognostic factors for DFS. Conclusions : Our results suggest that CD44s, but not CD44v6, plays a role in tumor progression and it could be a potential prognostic factor for patients with RCCs.

Differential Expression of CD34 and Smooth Muscle Actin in the Stroma of Small Lung Adenocarcinoma with Mixed Bronchioloalveolar and Invasive Components.: Mee Sook Roh, Jong Woo Choi, Hyoun Wook Lee, Hyuk Chan Kwon, Tae Ho Park, Phil Jo Choi, Chang Hun Lee, Bong Kwon Cheon; Korean J Pathol. 2005;39(3):158-163.

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Abstract PDF: BACKGROUND
Absence of CD34-positive fibroblasts was reported within the stroma associated with invasive carcinomas. Conversely, tumor-associated desmoplastic stroma is characterized by the presence of smooth muscle actin (SMA)-reactive myofibroblasts. The present study was undertaken in order to elucidate whether the different distributions of stromal CD34-positive fibroblasts and SMA-reactive myofibroblasts are sensitive or specific markers of tumor invasion in small lung adenocarcinomas.
METHODS
Immunohistochemical stainings for CD34 and SMA were done in 37 peripheral adenocarcinomas less than 3.0 cm in diameter, including 16 adenocarcinomas with bronchioloalveolar carcinoma (BAC) and invasive components (mixed), and 21 invasive adenocarcinomas without BAC components (invasive).
RESULTS
The fibroblasts within the BAC components of the mixed group were mainly CD34-positive (81.2%) and preferentially SMA-negative (56.3%). In contrast, the fibroblasts within the invasive components of the mixed group were mainly CD34-negative (75.0%) and SMApositive (87.5%). The stromal cells of the invasive group were mostly negative for CD34 (90.5%) and positive for SMA (95.3%).
CONCLUSIONS
The loss of CD34 and the acquisition of SMA in the stromal cells within the tumor were related to tumor invasion (p<0.05). Thus, expression patterns of CD34 and SMA can be used to detect small foci of early stromal invasion in adenocarcinomas of the lung.

Clinicopathologic Significance of CD44s, CD44v5 and CD44v6 Expression in Non Small Cell Lung Carcinomas.: Jae Kyun Kim, Chang Hun Lee, Kyeong Min Lee, Jin Mi Song; Korean J Pathol. 2004;38(2):93-99.

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Abstract PDF: BACKGROUND
CD44 is a polymorphic family of transmembrane glycoproteins generated by alternative splicing of messenger RNA and is involved in the mechanism of tumor invasion and metastasis.
METHODS
The expression of selected CD44 molecules (CD44s, CD44v5, and CD44v6) was determined immunohistochemically in 84 cases of non small cell lung carcinomas (NSCLCs). The results were compared with PCNA index, microvessel density (MVD), and clinicopathological parameters including patient? survival.
RESULTS
CD44s showed a positive reaction in 61.9% (52/84) of NSCLCs, CD44v5 in 73.8% (62/84), and CD44v6 in 39.3% (33/84). Squamous cell carcinomas (SCCs) displayed preferential expression of all CD44 molecules in comparison with adenocarcinomas (ACs) (p<0.001). As a whole, the expression of CD44 molecules was not correlated with clinical parameters (stage, TNM-T, and TNM-N), PCNA index, or MVD. For ACs only, however, CD44v5 expression was negatively correlated with PCNA index (p<0.05). Poor survival was correlated with CD44v5 expression in ACs and CD44v6 in SCCs (both, p<0.05).
CONCLUSIONS
These findings suggest that CD44 molecule in NSCLC could be a distinctive phenotypic marker for SCC, and the possibility that CD44v5 and CD44v6 are in some way instrumental in conditioning the biologic behavior of NSCLC according to major histologic types.

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