Differential expression of the novel oncogene, SALL4, in lymphoma, plasma cell myeloma, and acute lymphoblastic leukemia

Cui, Wei; Kong, Nikki R.; Ma, Yupo; Amin, Hesham M.; Lai, Raymond; Chai, Li

doi:10.1038/modpathol.3800694

Cited by 80 publications

(75 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the literature, the only other types of non-germ cell tumors that were immunohistochemically positive for SALL4 staining were precursor B-lymphoblastic lymphoma and acute myeloid leukemia, whereas other types of hematolymphoid tumors were negative. 30 Distinction of these tumors from germ cell tumors can usually be made on clinical presentation, morphologic findings, and, in difficult cases, immunohistochemistry for pan B cell or myeloid leukemia markers.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic utility of SALL4 in primary germ cell tumors of the central nervous system: a study of 77 cases

et al. 2009

View full text Add to dashboard Cite

Primary germ cell tumors of the central nervous system (CNS) sometimes pose diagnostic difficulty. In this study we analyzed the diagnostic utility of a novel marker, SALL4, in 77 such tumors (59 pure and 18 mixed) consisting of the following tumors/tumor components: 49 germinomas, 7 embryonal carcinomas, 27 yolk sac tumors, 3 choriocarcinomas, and 14 teratomas. We also stained SALL4 in 99 primary non-germ cell tumors to test SALL4 specificity. We compared SALL4 with OCT4 in all germ cell tumors and compared SALL4 with a-fetoprotein and glypican-3 in all yolk sac tumors. The staining was semiquantitatively scored as 0 (no staining), 1 þ (o ¼ 30%), 2 þ (31-60%), 3 þ (61-90%), and 4 þ (490%). Strong SALL4 staining was observed in all 49 germinomas (4 þ in 48, 3 þ in 1), 7 embryonal carcinomas (all 4 þ ), and 27 yolk sac tumors (1 þ in 1, 2 þ in 2, 3 þ in 7, 4 þ in 17). SALL4 staining, 1 þ weak to focally strong, was observed in 2 of 3 choriocarcinomas (in mononucleated trophoblasts) and in 9 of 14 teratomas (in primitive neuroepithelium and teratomatous glands). All germinomas and embryonal carcinomas showed strong OCT4 staining (4 þ in all except 1 germinoma with 3 þ ), whereas other germ cell tumors were negative. Out of 27 yolk sac tumors, 26 showed positive a-fetoprotein staining (1 þ in 9, 2 þ in 7, 3 þ in 5, and 4 þ in 5). All yolk sac tumors showed positive glypican-3 staining (1 þ in 6, 2 þ in 6, 3 þ in 7, and 4 þ in 8). The mean percentage of yolk sac tumor cells stained was 84% with SALL4, 45% with a-fetoprotein, and 63% with glypican-3 (Po0.01). No non-germ cell tumors showed SALL4 staining. Our results indicate that SALL4 is a novel sensitive diagnostic marker for primary germ cell tumors of the CNS with high specificity. SALL4 is a more sensitive marker than a-fetoprotein and glypican-3 for yolk sac tumors.

show abstract

Section: Discussionmentioning

confidence: 99%

Diagnostic utility of SALL4 in primary germ cell tumors of the central nervous system: a study of 77 cases

et al. 2009

View full text Add to dashboard Cite

show abstract

“…51,52 Morphologically, metastatic yolk sac tumor or other germ cell tumors should be easily distinguished from these entities. In difficult cases, an immunohistochemical panel including antibodies toward CD10, CD19, CD79a, and TDT for precursor B lymphoblastic lymphoma and myeloperoxidase, leukocyte common antigen (CD45), CD43, and CD34 for myeloid leukemia should help in making the distinction from germ cell tumor.…”

Section: Discussionmentioning

confidence: 99%

SALL4 is a novel sensitive and specific marker for metastatic germ cell tumors, with particular utility in detection of metastatic yolk sac tumors

Cao¹,

Humphrey²,

Allan³

2009

Cancer

143

115

View full text Add to dashboard Cite

BACKGROUND:The correct diagnosis of metastatic germ cell tumors is critical, because these tumors can be effectively treated and are even cured with modern therapy. Their histopathologic diagnosis can be challenging without immunohistochemical markers, which currently have limitations. SALL4 is a novel stem cell marker essential to maintain pluripotency and self‐renewal of embryonic stem cells. In the current study, the authors investigated the utility of SALL4 as a potential diagnostic marker for metastatic germ cell tumors.METHODS:Ninety metastatic germ cell tumors from testis, ovary, and extragonadal sites were stained with a monoclonal SALL4 antibody. In addition, 170 metastatic nongerm cell malignancies, including 158 carcinomas (6 head and neck, 8 thyroid, 12 lung, 8 breast, 7 hepatocellular, 3 cholangiocarcinomas, 2 ampullary, 10 pancreatic, 18 gastric, 15 esophageal, 10 renal cell, 10 urothelial, 12 prostatic, 18 ovarian, 6 uterine, and 13 colonic) and 12 melanomas, were also stained to test SALL4 specificity.RESULTS:All 22 seminomas, 7 dysgerminomas, 22 embryonal carcinomas, and 14 of 15 yolk sac tumors displayed strong and diffuse SALL positivity in >90% of tumor cells (80% of tumor cells were strongly positive in the remaining yolk sac tumor). Five of 7 choriocarcinomas and 9 of 18 teratomas were also variably positive for SALL4. In contrast, only 10 (esophageal, gastric, and colonic adenocarcinomas) of 170 metastatic somatic tumors demonstrated focally weak SALL4 reactivity (<25% tumor cells).CONCLUSIONS:SALL4 is a novel sensitive and highly specific marker for metastatic germ cell tumors, and is particularly useful for detecting metastatic yolk sac tumors. Cancer 2009. © 2009 American Cancer Society.

show abstract

“…In addition, SALL4 upregulates the expression of the oncogene Bmi-1 in human hematopoietic stem cells and leukemia cells (14). Numerous other studies have also revealed the oncogenic potential of SALL4 (5,6,15), indicating that SALL4 may be used as a diagnostic marker in human malignancies. However, there have been no studies investigating the sensitivity and specificity of SALL4 expression in the diagnosis of non-germ cell tumors (GCTs).…”

Section: Introductionmentioning

confidence: 98%

“…Currently, a considerable number of stem cell-associated markers have been identified (2,3). Numerous studies have revealed that Sal-like protein 4 (SALL4) and leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) are also involved in the tumorigenesis, development and metastasis of various tumors (5)(6)(7), and these proteins are expected to become potential diagnostic markers and therapeutic targets in cancer.…”

Section: Introductionmentioning

confidence: 99%

Expression and clinical significance of SALL4 and LGR5 in patients with lung cancer

et al. 2015

View full text Add to dashboard Cite

Abstract. Lung cancer is the most frequent cancer worldwide, in terms of incidence and mortality. Due to challenges in the diagnosis of the disease, the 5-year overall survival rate is only ~16%. Previous studies have suggested that malignant transformations originate from adult stem cells, and malignant lesions may therefore express stem-cell-associated markers. The purpose of the present study is to investigate the expression and clinical significance of the stem cell-associated markers Sal-like protein 4 (SALL4) and leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) in lung cancer, and to provide novel diagnostic markers and targets for the treatment of lung cancer. The expression of the stem cell-associated markers SALL4 and LGR5 was analyzed by immunohistochemistry performed on 135 human lung cancer tissue specimens and 10 non-cancer lung tissue specimens. The clinical significance of the expression of these markers and correlation between their expression and clinical parameters was also assessed. SALL4 expression was highly upregulated in lung cancer tissues, but was not present in non-cancerous lung tissues, and the sensitivity and specificity of SALL4 reached 88% and 100%, respectively. By contrast, LGR5 demonstrated 97% sensitivity, but the specificity was poor. Therefore, SALL4 may be an extremely useful diagnostic marker for lung cancer, but LGR5 is not as useful. IntroductionLung cancer is the most common cancer worldwide, in terms of incidence and mortality, as it comprises 17% of total novel cancer cases and 23% of the total global cancer mortalities (1). In order to improve the survival rate, it is important to diagnose and surgically excise lung cancer at an early stage of disease (2). Therefore, it is necessary to identify biomarkers with the potential to facilitate tumor diagnosis, particularly in the early stages of the disease. The cancer stem cell (CSC) theory proposes that tumors contain a small subpopulation of CSCs, which are responsible for tumor growth, invasion and metastasis (2). CSCs and normal tissue stem cells share important characteristics, including self-renewal, multipotency and unlimited proliferation, and potentially possess overlapping molecular mechanisms (3,4). Currently, a considerable number of stem cell-associated markers have been identified (2,3). Numerous studies have revealed that Sal-like protein 4 (SALL4) and leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) are also involved in the tumorigenesis, development and metastasis of various tumors (5-7), and these proteins are expected to become potential diagnostic markers and therapeutic targets in cancer.SALL4, a homolog of the Drosophila homeotic gene spalt, is a zinc-finger transcription factor that is required for the proliferation and maintenance of pluripotency through interaction with OCT3/4, sex determining region Y-box 2 and NANOG (8,9). SALL4 is also highly expressed in embryonic stem cells (8)(9)(10)(11)(12). Notably, SALL4 is also overexpressed in various types of human he...

show abstract

Differential expression of the novel oncogene, SALL4, in lymphoma, plasma cell myeloma, and acute lymphoblastic leukemia

Cited by 80 publications

References 34 publications

Diagnostic utility of SALL4 in primary germ cell tumors of the central nervous system: a study of 77 cases

Diagnostic utility of SALL4 in primary germ cell tumors of the central nervous system: a study of 77 cases

SALL4 is a novel sensitive and specific marker for metastatic germ cell tumors, with particular utility in detection of metastatic yolk sac tumors

Expression and clinical significance of SALL4 and LGR5 in patients with lung cancer

Contact Info

Product

Resources

About