Dataset Information

Immunohistochemistry for Diagnosis of Metastatic Carcinomas of Unknown Primary Site.

ABSTRACT: Immunohistochemistry has become an essential ancillary examination for the identification and classification of carcinomas of unknown primary site (CUPs). Over the last decade, the diagnostic accuracy of organ- or tumour-specific immunomarkers and the clinical validation of effective immunohistochemical panels has improved significantly. When dealing with small sample sizes, diagnostic accuracy is crucial, particularly in the current era of targeted molecular and immune-based therapies. Effective systematic use of appropriate immunohistochemical panels enables accurate classification of most of the undifferentiated carcinomas as well as careful preservation of tissues for potential molecular or other ancillary tests. This review discusses the algorithmic approach to the diagnosis of CUPs using CK7 and CK20 staining patterns. It outlines the most frequently used tissue-specific antibodies, provides some pitfalls essential in avoiding potential diagnostic errors and discusses the complementary tools, such as molecular tumour profiling and mutation-specific antibodies, for the improvement of diagnosis and prediction of the treatment response.

SUBMITTER: Selves J

PROVIDER: S-EPMC5923363 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Immunohistochemistry for Diagnosis of Metastatic Carcinomas of Unknown Primary Site.

Selves Janick J Long-Mira Elodie E Mathieu Marie-Christine MC Rochaix Philippe P Ilié Marius M

Cancers 20180405 4

Immunohistochemistry has become an essential ancillary examination for the identification and classification of carcinomas of unknown primary site (CUPs). Over the last decade, the diagnostic accuracy of organ- or tumour-specific immunomarkers and the clinical validation of effective immunohistochemical panels has improved significantly. When dealing with small sample sizes, diagnostic accuracy is crucial, particularly in the current era of targeted molecular and immune-based therapies. Effectiv ...[more]

PMID: 29621151

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Project description:BackgroundMetastatic adenocarcinoma of unknown primary site (MACUP) is the most common cancer of unknown primary site, and shows worse prognosis. Prediction of its tumor site origin attracts a growing attention. However, the site determined by gene expression profiling does not have a significant impact on the survival. Some other special method might need to be found out.MethodsWe reviewed 1011 MACUP patients diagnosed by pathological examination and immunohistochemistry based on the Surveillance, Epidemiology, and End Results (SEER) database during 2010-2016. Kaplan-Meier curves and Cox proportional hazard model were analyzed to compare the survival. Logistic regression models and relevant nomograms were performed to predicting the probability of the primary site which including digestive system, respiratory system, and female breast. The validation and clinical utility of models were measured with relevant statistical approaches.ResultsAbout 324 (32.1%), 299 (29.6%), and 203 (20.1%) of MACUP patients were identified as the primary sites of digestive system, respiratory system, and female breast, respectively. Patients derived from digestive system and respiratory system showed poorer survival than these with other sites. Digestive system was significantly associated with liver (Odds ratio =13.21 [95% confidence interval =8.48-21.02]) or lung (2.36 [1.40-3.97]) metastasis, while respiratory system was linked to brain (11.68 [6.68-21.26]) or lymph node (3.39 [2.26-5.13]) metastasis. Patients identified as female breast were prone to occur bone metastasis (5.85 [3.68-9.45]). Logistic regression nomograms were developed to help clinicians intuitively predict the probabilities of tumor site origin with 0.867, 0.824, and 0.753 of the C-index, respectively. Decision curve analysis and clinical impact curves both revealed the clinical effectiveness.ConclusionsWe profiled different tumor site origin of MACUP patients and established prediction models. These features might be significant for clinicians to improve the probabilities of predicting the primary sites, and to decide subsequent treatment strategy.

Project description:To determine if immunohistochemistry is useful to distinguish between primary and metastatic hepatic carcinoma.Cases of hepatocellular and adenocarcinoma of liver from surgical and autopsy pathology files as diagnosed on routine histopathology with the help of haematoxylin-eosin stain.Thirty four patients with hepatic space - occupying lesions (a single lesion in 6 patients, multiple lesions in 5 patients and unspecified in remaining 23 patients). The histopathology diagnosis included 14 hepatocellular carcinoma (HC), 10 cholangiocarcinoma (CC), 7 metastatic carcinoma (MC) (colonic: n=4, pancreatic: n=2, mammary: n=l) and three cases were unclassified.The paraffin embedded blocks of biopsy and autopsy cases were taken out and sections of 4 µm thickness were cut. The immunohistochemistry staining was carried out by using a panel of 7 monoclonal antibodies. The monoclonal antibodies which were used were as follows - a fetoprotein (AFP), α 1 antitrypsin (AAT), monoclonal carcinoembryonic antigen (MCEA), myelomonocytic antigen (Leu-Ml), tumour associated glycoprotein (B72-3), A-subunit coagulation Factor XIII (Factor XIIIa) and blood group substance (Lex).Sections were defined as immunohistochemically 'positive' if definitive crisp labelling was seen in atleast 10% of tumour cells by two observers. The positive staining was classified as either predominantly cytoplasmic or membranous or both. The presence or absence of nuclear staining was also noted.The typical immunoreactivity of HCs included positivity for AAT, AFP and factor XIIIa and no staining for B 72-3 and Leu-Ml. Of 14 patients who were originally diagnosed as having HC, AAT was expressed in 86% and AFP was expressed in cytoplasm in half of the patients. Factor XIIIa displayed cytoplasmic reactivity in 71% cases of HC. Lex was present focally in 3 cases of HC, as was monoclonal CEA. These 3 cases showed features of hepatocholangiocarcinoma. In all 10 cases of CC there was staining for both Leu-Ml and Lex. The pattern of reactivity was cytoplasmic for Leu-Ml and it was both cytoplasmic and membranous for Lex. In 6 cases there was expression of B72-3 and monoclonal CEA in cytoplasm. None of the cases of CC showed staining for AFP and AAT only one case showed staining for AAT and factor XIIIa. As far as MC is concerned, there was expression of both Leu-M, and Lex in a cytoplasmic distribution in all the seven cases. The membranous accentuation of Lex seen in all cases of CC was not present in the cases of MC. Four of the 7 cases of MC showed reactivity for B72-3 as well and the staining pattern of Leu-M, and B72-3 was predominantly both cytoplasmic and membranous. In 3 of the 7 cases of MC, there was expression of monoclonal CEA, in 1 case there was expression of AAT and in 2 cases there was expression of factor XIIIa.Histologic differentiation of HC from CC and MC can be greatly aided by immunohistochemical studies. Using a panel of 7 antibodies, cases of HC displayed cytoplasmic reactivity for AAT, AFP and factor XIIIa. Cases of CC showed membranous and cytoplasmic reactivity for Lex but only cytoplasmic reactivity for Leu-M, and B72-3. On the other hand cases of MC showed only cytoplasmic staining but not membranous accentuation for Lex but Leu-M, and B72-3 showed membranous as well as cytoplasmic staining. The antibody MCEA showed variable results and hence was considered not useful. Therefore the results strongly suggest that a panel of 6 monoclonal antibodies (except MCEA) will greatly help in differentiating between primary and metastatic carcinoma.

Project description:BACKGROUND:Cancer of unknown primary (CUP) is a late-stage malignancy with poor prognosis, but we know little about what diagnostic tests and procedures people with CUP receive prior to diagnosis. The purpose of this study was to determine how health service utilisation prior to diagnosis for people with cancer-registry notified CUP differs from those notified with metastatic cancer of known primary. METHODS:We identified people with a cancer registry notification of CUP (n = 327) from the 45 and Up Study, a prospective cohort of 266,724 people ?45 years in New South Wales, Australia, matched with up to three controls with a diagnosis of metastatic cancer of known primary (n = 977). Baseline questionnaire data were linked to population health data to identify all health service use, diagnostic tests, and procedures in the month of diagnosis and 3 months prior. We used conditional logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS:After adjusting for age and educational attainment, people with a cancer-registry notified CUP diagnosis were more likely to be an aged care resident (OR = 2.78, 95%CI 1.37-5.63), have an emergency department visit (OR = 1.65, 95%CI 1.23-2.21), serum tumor marker tests (OR = 1.51, 95%CI 1.12-2.04), or a cytology test without immunohistochemistry (OR = 2.01, 95%CI 1.47-2.76), and less likely to have a histopathology test without immunohistochemistry (OR = 0.43, 95%CI 0.31-0.59). Neither general practitioner, specialist, allied health practitioner or nurse consultations, hospitalisations, nor imaging procedures were associated with a CUP diagnosis. CONCLUSIONS:The health service and diagnostic pathway to diagnosis differs markedly for people notified with CUP compared to those with metastatic cancer of known primary. While these differences may indicate missed opportunities for earlier detection and appropriate management, for some patients they may be clinically appropriate.

Dataset Information

Immunohistochemistry for Diagnosis of Metastatic Carcinomas of Unknown Primary Site.

Publications

Immunohistochemistry for Diagnosis of Metastatic Carcinomas of Unknown Primary Site.

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