Abstract:- A stepwise approach to the evaluation of fine-needle aspiration and small biopsy tissue specimens in conjunction with a small panel of select immunohistochemical stains has been successful in accurately assessing the lineage/origin of the metastatic tumors of unknown primaries. The awareness of the common pitfalls of these biomarkers is essential in many instances.
“…In contrast, mesenchymal tumours and hematopoietic neoplasms may express epithelial markers. A pitfall to keep in mind is that poorly fixed specimens may have an unpredictable pattern of staining for CK [ 4 , 9 , 82 ].…”
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.
“…In contrast, mesenchymal tumours and hematopoietic neoplasms may express epithelial markers. A pitfall to keep in mind is that poorly fixed specimens may have an unpredictable pattern of staining for CK [ 4 , 9 , 82 ].…”
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.
“…1 ). If epithelial origin of the lesion is confirmed (CK+ , S100−, vimentin ± and LCA−), a combination of CK7 and CK20 will give a first indication of the organ in which the tumour is most likely to have originated [ 29 ]. Fig.…”
Cancer of unknown primary (CUP) is defined as a heterogeneous group of tumours that present with metastasis, and in which attempts to identify the original site have failed. They differ from other primary tumours in their biological features and how they spread, which means that they can be considered a separate entity. There are several hypotheses regarding their origin, but the most plausible explanation for their aggressiveness and chemoresistance seems to involve chromosomal instability. Depending on the type of study done, CUP can account for 2–9% of all cancer patients, mostly 60–75 years old. This article reviews the main clinical, pathological, and molecular studies conducted to analyse and determine the origin of CUP.
The main strategies for patient management and treatment, by both clinicians and pathologists, are also addressed.
“…In recent decades, IHC staining has become important part of diagnosis of various type of undifferentiated neoplasms [11]. Several IHC biomarkers, such as Wilms' tumor protein (WT1), proliferation marker (Ki67), p53 protein, epidermal growth factor receptor (EGFR), glial fibrillary acidic protein (GFAP), vimentin, have been investigated for different types of brain tumors [12,15,[17][18][19].…”
Section: Discussionmentioning
confidence: 99%
“…Immunohistochemical (IHC) staining is powerful method which can reveal the biologic behavior of the neoplasms and thus will give useful prognostic information such as survival association and tumor recurrence for patients with astrocytic brain tumor [11]. Previous biomarker studies have investigated only one or two potential biomarkers in tumor samples from patients with glioblastoma and identified their relationship with prognosis and correlation with other biomarkers [12][13][14][15].…”
Objectives: Astrocytoma is a common primary malignant brain tumor and it is typically associated with poor outcome. In this study, we aimed to determine role of various immunohistochemical (IHC) biomarkers and their relationship with patient prognosis. Methods: Patients who underwent surgery for astrocytic brain tumor were selected. Tissue specimens were collected from surgically removed tumors and stained by various IHC stains. All-cause mortality was chosen for study endpoint. Results: A total of 133 patients with who underwent surgery for astrocytic brain tumor were included (mean age 38±19 and 49.6% male). During follow-up, 84 patients (63%) died and the median time of death was 8 months (IQR 4; 16) after hospital discharge. Patients who died had higher tumor grade (60.7% vs. 34.7%, p<0.01). After adjustment of possible predictors, surgical type (HR=0.51, 95% CI 0.31-0.82, p<0.01), expression level of Ki67 (HR=1.02, 95% CI 1.00-1.04, p<0.05) and p53 (HR=1.01, 95% CI 1.00-1.02, p<0.05) were independently associated with long term mortality. Kaplan-Meier estimation showed overexpression of WT1 (42% vs. 52%, p<0.05) and Ki67 (27% vs. 58%, p<0.001) are associated with poor survival. Conclusion: IHC biomarkers are independently associated with long term prognosis in patients with astrocytic brain tumor. Overexpression of WT1 and Ki67 marker are associated with poor survival.
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