open access: PLoS ONE: Immunohistochemical Profile for Unknown Primary Adenocarcinoma (CUP) (lung, digestive, gynecologic, prostate, liver, kidney, breast, urothelial, unclassified)

Background

Development of tailored treatment based on immunohistochemical profiles (IPs) of tumors for cancers of unknown primary is needed.

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The primary tumor sites based on the immunohistochemical profiles (IPs) for the 71 unknown primary patients were the lung for 17 patients, digestive organs for 13, gynecological organs for 9, prostate for 7, liver/kidney for 6, breast for 4, urothelial for 2, and were not unclassified for 13 patients (Table 2).Figures 2 and 3 show typical IHC results for the breast and lung profiles.

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Methodology/Principal Findings

"We developed an algorithm based on primary known adenocarcinoma for testing sensitivity and specificity. Formalin-fixed paraffin-embedded tissue samples from 71 patients of unfavorable subsets of unknown primary adenocarcinoma were obtained. We examined 15 molecular markers using the algorithm incorporating these IPs and classified the tumours into 9 subsets based on the primary tumour site. The sensitivity and specificity of this algorithm were 80.3% and 97.6%, respectively."

"Apparent primary sites were lung in 17 patients, digestive organs in 13, gynecological organs in 9, prostate in 7, liver or kidney in 6, breast in 4, urothelial organ in 2, biliary tract and pancreatic profile in none, and unclassified in 13."

Response evaluation (treatment plan) and survival analysis:

"...... Response rates by profile are listed in Table 2. A higher response rate was observed for the gynecological profile (67%) than for the other profiles...."

Discussion:

"...Further, we consider gynecologic profile may not be necessary to be classified into ovary, endometrial, and cervical adenocarcinoma in the situation of adenocarcinoma of unknown primary because chemotherapies for these cancer become similar in advanced disease [32], [33]..."

The algorithm we generated for orienting primary has value:

"Immunohistochemistory is generally done in routine work for the diagnosis of adenocarcinoma of unknown primary in many cancer centers. Therefore, there is no additional skill or tool in the procedure of diagnosis [10], [25]."

"This study has some limitations. First, the prognostic value of each IP was potentially underpowered, as the number of patients in each subgroup was somewhat small, not allowing the response rate, PFS, and OS to be compared to historical control data. Second, the results need to be validated in a prospective manner by applying standard treatments for identified primary profiles, to go beyond simply identifying prognostic factors for unknown primary adenocarcinoma....

"In this study, we revealed the prognostic value of a panel composed of immunohistochemistry profiles for patients with adenocarcinoma of unknown primary who received platinum doublet chemotherapy. Orienting primary sites either IHC or cDNA microarray in patients with CUPs is not good enough, we need to examine survival benefit when applying organ-oriented standard chemotherapies for patients with CUPs.
Our results may encourage a prospective randomized trial to compare standard platinum doublet chemotherapy with treatment determined by the IP. This approach may assist in developing new treatment strategy compared to a single arm platinum combination trial"