Classification using hierarchical clustering of tumor-infiltrating immune cells identifies poor prognostic ovarian cancers with high levels of COX expression

Liu, Min; Matsumura, Noriomi; Mandai, Masaki; Li, Kui; Yagi, Haruhiko; Baba, Tsukasa; Suzuki, Ayako; Hamanishi, Junzo; Fukuhara, Ken; Konishi, Ikuo

doi:10.1038/modpathol.2008.187

Cited by 34 publications

(38 citation statements)

References 52 publications

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“…More recently, studies of protein expression, including ours, have taken advantage of this method. 23,24 The hierarchical clustering detected the mutually exclusive pattern of CK7 and DPEP1 (Figure 2c). Therefore, a combination of CK7 and DPEP1 staining is expected to distinguish ovarian metastases of colorectal cancers from primary mucinous ovarian carcinomas very accurately.…”

Section: Diagnosis Of Ovarian Metastasismentioning

confidence: 97%

Distinguishing primary from secondary mucinous ovarian tumors: an algorithm using the novel marker DPEP1

et al. 2011

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Distinguishing primary mucinous ovarian cancers from ovarian metastases of digestive organ cancers is often challenging. Dipeptidase 1 was selected as the candidate novel marker of colorectal cancer based on an analysis of a gene expression microarray. Immunohistochemical analysis indicated that 13/16 ovarian metastases of colorectal cancers, but only 1/58 primary mucinous ovarian cancers, were dipeptidase 1-positive (threshold;^25% expression, Po0.0001). Next, five immunohistochemical markers (dipeptidase 1, estrogen receptor-a, cytokeratin 7, cytokeratin 20, and caudal type homeobox 2) were analyzed in combination. In a hierarchical clustering analysis, the mutually exclusive expression of cytokeratin 7 and dipeptidase 1 specifically identified the ovarian metastases of colorectal cancers (Po0.0001). In a decision tree analysis, cytokeratin 7, caudal type homeobox 2, and dipeptidase 1 classified primary mucinous ovarian cancers and ovarian metastases of digestive organ cancers with 90% accuracy. Finally, the five immunohistochemical markers were combined with six preoperative factors (patient's age, tumor size, laterality, serum CEA, CA19-9, and CA125) and combinations were analyzed. Of the 11 factors, 4 (dipeptidase 1, cytokeratin 7, caudal type homeobox 2, and tumor size) were used to generate a decision tree to classify primary mucinous ovarian cancers and metastases of digestive organ cancers with 93% accuracy. In conclusion, we identified a novel immunohistochemical marker, dipeptidase 1, to distinguish primary mucinous ovarian cancers from ovarian metastasis of colorectal cancers. The algorithm using immunohistochemical and clinical factors to distinguish metastases of digestive organ cancers from primary mucinous ovarian cancers will be useful to establish a protocol for the diagnosis of ovarian metastasis. Modern Pathology (2011) 24, 267-276; doi:10.1038/modpathol.2010; published online 12 November 2010 Keywords: differential diagnosis; dipeptidase 1(DPEP1); metastasis; mucinous adenocarcinoma; ovaryThe ovary is a common site of metastasis, 1 and in many cases, there is a known history of primary tumors outside the ovary. However, ovarian masses are sometimes found in patients with no known history of malignancy and the primary tumor is not diagnosed until some time later. The morphology of a metastatic tumor in the ovary can mimic a primary ovarian tumor by a so-called maturation phenomenon. 2 A majority of the tumors exhibit cystic pattern when they metastasize to the ovary, whereas primary tumor in the original site is not cystic at all. Furthermore, many metastatic mucinous adenocarcinomas, especially from digestive organ cancers, contain a mixture of mucinous epithelium with a range of atypia, resembling primary mucinous carcinomas or borderline tumors. Many metastatic mucinous carcinomas of the ovary have been and continue to be misdiagnosed as primary ovarian mucinous adenocarcinomas. 3

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Section: Diagnosis Of Ovarian Metastasismentioning

confidence: 97%

Distinguishing primary from secondary mucinous ovarian tumors: an algorithm using the novel marker DPEP1

et al. 2011

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“…17 Similar results have been reported extensively elsewhere. [18][19][20][21][22][23][24][25][26][27][28][29][30][31] Three other studies indicate that both CD3 and CD8C TILs are of good prognosis in ovarian cancer. [32][33][34] While CD8C TILs appear to be best associated with improved survival, still other reports indicate that CD4C TILs are the subset of value in prognosticating ovarian cancer.…”

Section: Background On Tumor Infiltrating Lymphocytesmentioning

confidence: 99%

Tumor infiltrating lymphocytes in ovarian cancer

Santoiemma

Powell

2015

Cancer Biology & Therapy

295

229

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The accumulation of tumor infiltrating lymphocytes (TILs) in ovarian cancer is prognostic for increased survival while increases in immunosuppressive regulatory T-cells (Tregs) are associated with poor outcomes. Approaches that bolster tumor-reactive TILs may limit tumor progression. However, identifying tumor-reactive TILs in ovarian cancer has been challenging, though adoptive TIL therapy in patients has been encouraging. Other forms of TIL immunomodulation remain under investigation including Treg depletion, antibody-based checkpoint modification, activation and amplification using dendritic cells, antigen presenting cells or IL-2 cytokine culture, adjuvant cytokine injections, and geneengineered T-cells. Many approaches to TIL manipulation inhibit ovarian cancer progression in preclinical or clinical studies as monotherapy. Here, we review the impact of TILs in ovarian cancer and attempts to mobilize TILs to halt tumor progression. We conclude that effective TIL therapy for ovarian cancer is at the brink of translation and optimal TIL activity may require combined methodologies to deliver clinically-relevant treatment. IntroductionTumor infiltrating lymphocytes (TILs) are present in ovarian cancer and are prognostic for increased survival. Given the impact of immunomodulatory regimens in melanoma, renal cell carcinoma, and lung cancer, and the recent elucidation of bona fide tumor-reactive TILs in ovarian cancer, the development of approaches that mobilize tumor-reactive TILs for successful eradication of ovarian cancer is now a high priority. In spite of strong rationale, attempts at administration of adoptive T cell transfer, immune enhancing antibody, and tumor immune environment conditioning in ovarian cancer have been minimal with some positive results reported in patients. In light of the recent development of new immunotherapeutic agents and treatment regimens that bolster host TIL activity, we review the current understanding of the immunobiology of human ovarian cancer including the impact of TIL subset accumulation on ovarian cancer survival and the effect of immune activation in the tumor microenvironment, and conclude that a new line of cancer immunotherapy investigations is warranted in ovarian carcinoma.Ovarian cancer is the second most common and most lethal gynecologic malignancy in the United States with approximately 22,000 new cases and 14,000 deaths expected in 2013.1 Ovarian cancer is often diagnosed at an advanced stage, with the large majority of new cases spread past the primary site. Since there are no current recommendations for ovarian cancer screenings, most efforts at combating ovarian cancer have been targeted at the discovery of new treatments rather than preventative measures. Currently, surgical staging and cytoreduction followed by chemotherapy is the mainstay of treatment, although in some cases neo-adjuvant chemotherapy is attempted.2 The standard for surgical staging consists of total hysterectomy and bilateral salpingooophrectomy with pelvic and para-aortic lymph node di...

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“…these immune cells and cytokines also correlate with tumor progression and prognosis in various cancers. (6)(7)(8). plasma levels of cytokines such as interleukin (Il)-10, Il-12, Il-18 and tumor necrosis factor (tnF)-α are prognostic markers of various cancers (9-11).…”

Section: T Cells To Cd57mentioning

confidence: 99%

Altered cytokine levels and increased CD4+CD57+ T cells in the peripheral blood of hepatitis C virus-related hepatocellular carcinoma patients

et al. 2011

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+ αβtcr + cells (cD57 + t cells), showed a significant inverse correlation with pB-IFn-γ-producing capability. the present results suggest that an increase in cD4 + cD57 + t cells controls the capability of pB to produce the antitumor cytokine IFn-γ and that pB-IFn-γ production is impaired with Hcc tumor progression. IntroductionHepatocellular carcinoma (HCC) is the fifth most common cancer in men and the eighth most common cancer in women worldwide. Hcc is highly prevalent in patients with chronic liver diseases resulting mainly from hepatitis B virus (HBV) or hepatitis c virus (HcV) infection, and its incidence is now increasing. In Japan, Hcc is the third most common cause of mortality, and the most frequent cause of Hcc is chronic infection with HcV (1,2 A b b re vi a t i o n s:A lt, a la n i n e t r a n s a m i n a s e; A F p, α

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Classification using hierarchical clustering of tumor-infiltrating immune cells identifies poor prognostic ovarian cancers with high levels of COX expression

Cited by 34 publications

References 52 publications

Distinguishing primary from secondary mucinous ovarian tumors: an algorithm using the novel marker DPEP1

Distinguishing primary from secondary mucinous ovarian tumors: an algorithm using the novel marker DPEP1

Tumor infiltrating lymphocytes in ovarian cancer

Altered cytokine levels and increased CD4+CD57+ T cells in the peripheral blood of hepatitis C virus-related hepatocellular carcinoma patients

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