Site‐specific cancer deaths in cancer of unknown primary diagnosed with lymph node metastasis may reveal hidden primaries

Hemminki, Kari; Bevier, Melanie; Sundquist, Jan; Hemminki, Akseli

doi:10.1002/ijc.27678

Cited by 22 publications

(21 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Identification of the primary malignancy is important because this influences therapy 12. Such therapy may therefore expedited by immediate biopsy.…”

Section: Discussionmentioning

confidence: 99%

Management of patients with uveal metastases at the Liverpool Ocular Oncology Centre

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Identification of the primary malignancy is important because this influences therapy 12. Such therapy may therefore expedited by immediate biopsy.…”

Section: Discussionmentioning

confidence: 99%

Management of patients with uveal metastases at the Liverpool Ocular Oncology Centre

et al. 2013

View full text Add to dashboard Cite

show abstract

“…In many countries, deaths due to breast cancer are mostly associated with metastatic disease [2]. Epithelialmesenchymal transition (EMT) has been proposed as an essential early step in tumor metastasis and breast carcinoma progression.…”

Section: Introductionmentioning

confidence: 99%

Membrane-Initiated Estradiol Signaling of Epithelial-Mesenchymal Transition-Associated Mechanisms Through Regulation of Tight Junctions in Human Breast Cancer Cells

et al. 2014

View full text Add to dashboard Cite

Tumor cells utilize inappropriate epithelialmesenchymal transition (EMT) mechanisms during the invasive process. It is becoming increasingly clear that estradiol (E2) induces breast cancer cell progression and enhances EMT; however, the mechanisms associated with this are unclear. We investigated the role of E2 on the expression and intracellular localization of the tight junction (TJ)-associated proteins, zonula occluden 1 (ZO-1), ZO-1-associated nucleic acid binding (ZONAB), and occludin, on the activation of cSrc and human epidermal growth factor receptor 2 (HER2) expression and cellular migration in the estrogen receptor (ER)-positive breast cancer cell lines, MCF-7 and T47D. WeNovelty and Impact Statements We demonstrated that estrogen is able to induce tight junction (TJ) disruption in two breast cancer cell lines through the activation of c-Src. Ablated expression of the novel epithelial marker CRB3 could lead to increased cell migration. Based on our findings, we propose a novel estrogen-induced TJ pathway associated with breast cancer cell motility and, eventually, to metastasis. demonstrated that 1 nM E2 elicits c-Src activation after 15 min. The p-Src/ZO-1 complex led to ZO-1 and ZONAB disruption at the TJ and increased expression of HER2 mRNAs. These changes correlate with decreased expression of the epithelial markers occludin and CRB3 and increased synthesis of N-cadherin. This led to increased MCF-7 cell migration induced by E2, even in the presence of a cell proliferation inhibitor. Incubation with ICI 182,780 (Fulvestrant), an ER antagonist, precluded the effects of E2 on c-Src phosphorylation, p-Src/ZO-1 complex formation, ZO-1/ZONAB nuclear translocation, and migration of MCF-7 cells. Our findings suggest that E2 promotes TJ disruption during tumor progression and increases cell motility. We propose a novel pathway where estrogens promote EMTassociated mechanisms that possibly lead to metastasis.

show abstract

“…Diagnoses were based on International Classification of Diseases (ICD) codes 7, 9 and 10, the latter two were particularly useful because they included the anatomic site where metastases were found. These included "unspecified CUP" (ICD-9 code 1990-1991, CUP often spread to multiple organs), "liver CUP" with liver metastasis, "lung CUP" with lung involvement (including thorax and lymph nodes and organs, brain and bone, for which lung cancer is usually given as the cause of death in CUP patients 7,8 ), "abdominal CUP" with abdominal metastases (including ovary) and "other CUP" with other metastatic locations (any other specified site). Histology was adenocarcinoma in 82.1%, squamous cell carcinoma in 5.0% and melanoma in 8.8% of the cases: 4.1% had miscellaneous or missing histology.…”

mentioning

confidence: 99%

Smoking and body mass index as risk factors for subtypes of cancer of unknown primary

et al. 2014

View full text Add to dashboard Cite

Cancer of unknown primary site (CUP) accounts for 3-5% of all cancer but because it is a fatal disease it ranks high among causes of cancer deaths. It has been called "an orphan disease" because it is diagnosed through metastatic tissue and the primary tumor often remains undetected. Based on autopsy data, the most common primaries were lung (27%), pancreas (24%), liver/bile (8%) and kidney/adrenals (8%). 1 CUP can be called "orphan disease" also because, as a metastatic disease, it is disregarded as a cancer entity when only primary cancers are considered. Thus, hardly anything is known about the underlying causes or risk factors. A recent European study published in this Journal showed that heavy smoking causes a risk of 3.66 for CUP patients of diverse and unspecified histologies; alcohol drinking and wide waist circumference were borderline risk factors. 2 The pathophysiology of CUP has remained an enigma, exemplified by the question presented in a review on CUP: "unknown primary or unknown biology?" 3 The inability to find a primary tumor may not merely depend on its small size but may involve newly described cell biological processes related to stem cell characteristics, microenvironment, immunoediting and senescence-apoptosis which may halt tumor growth and induce phenotypic changes. [3][4][5] In essence, an increased understanding of the interplay of host and tumor during the protracted process of carcinogenesis has made CUP less of a conundrum and more as a learning opportunity, in a 21st century parallel to the cancer biology gains provided by unravelling of several hereditary cancer syndromes in the previous century. Our recent studies support these data and suggest that the lung is a more common primary tissue than what the earlier data show. [6][7][8] In the present letter, we extend the study of Kaaks et al. addressing the question of tobacco smoking and body mass index (BMI) as risk factors of site-specific CUP, that is, by location of the diagnosed metastasis. 2 We hypothesize that smoking would have an effect on sites where smoking risks are highest among primary cancers, that is, lung. Patients and cancer-free controls were recruited from three Swedish prospective biobanks, the Umea Medical Biobank with 203 CUP patients and 1015 controls and the Malmo Diet and Cancer Study and the Prevention Study, jointly with 272 CUP patients and 1360 controls; 9 the controls were frequency matched on sex and age at interview. In Umea, the mean age at sampling was 57 years and at diagnosis it was 66 years; in Malm€ o, the respective ages were 51 and 71 years. Cancers were identified up to year 2012 through the regional Oncology Centers. Diagnoses were based on International Classification of Diseases (ICD) codes 7, 9 and 10, the latter two were particularly useful because they included the anatomic site where metastases were found. These included "unspecified CUP" (ICD-9 code 1990-1991, CUP often spread to multiple organs), "liver CUP" with liver metastasis, "lung CUP" with lung involvement (including thorax ...

show abstract

Site‐specific cancer deaths in cancer of unknown primary diagnosed with lymph node metastasis may reveal hidden primaries

Cited by 22 publications

References 32 publications

Management of patients with uveal metastases at the Liverpool Ocular Oncology Centre

Management of patients with uveal metastases at the Liverpool Ocular Oncology Centre

Membrane-Initiated Estradiol Signaling of Epithelial-Mesenchymal Transition-Associated Mechanisms Through Regulation of Tight Junctions in Human Breast Cancer Cells

Smoking and body mass index as risk factors for subtypes of cancer of unknown primary

Contact Info

Product

Resources

About