Assessment of BRAF V600E Status in Colorectal Carcinoma: Tissue-Specific Discordances between Immunohistochemistry and Sequencing.

Although sequencing provides the gold standard for identifying colorectal carcinoma with BRAF V600E mutation, immunohistochemistry (IHC) with the recently developed mouse monoclonal antibody VE1 for BRAF V600E protein has shown promise as a more widely available and rapid method. However, we identified anecdotal discordance between VE1 IHC and sequencing results and therefore analyzed VE1 staining by two different IHC methods (Leica Bond and Ventana BenchMark) in whole tissue sections from 480 colorectal carcinomas (323 BRAF wild-type, 142 BRAF V600E mutation, and 15 BRAF non-V600E mutation). We also compared the results with melanomas and papillary thyroid carcinomas (PTC). With the Bond method, among 142 BRAF V600E-mutated colorectal carcinomas, 77 (54%) had diffuse VE1 staining and 48 (33%) had heterogeneous staining, but 17 (12%) were negative. Among 323 BRAF wild-type colorectal carcinomas, 196 (61%) were negative, but 127 (39%) had staining, including 7 with diffuse staining. When positivity was defined as staining in ≥ 20% of tumor cells, VE1 IHC had sensitivity of 75% and specificity of 93% for BRAF V600E mutation. With the Ventana method, among 57 BRAF V600E-mutated colorectal carcinomas, 36 (63%) had diffuse VE1 staining, whereas 6 (11%) had no or weak (<20% of tumor cells) staining. Among 33 BRAF wild-type colorectal carcinomas, 16 (48%) had no or weak staining, whereas 15 (45%) had heterogeneous staining. In contrast with colorectal carcinoma, Bond and Ventana VE1 IHC in melanoma and PTC were highly concordant with sequencing results. We conclude that VE1 IHC produces suboptimal results in colorectal carcinoma and should not be used to guide patient management.

Bone invasion by adenoid cystic carcinoma of the lacrimal gland: preoperative imaging assessment and surgical considerations.

PURPOSE: To identify the incidence of radiologically and histologically documented bony invasion of the lacrimal gland fossa by adenoid cystic carcinoma. PATIENTS AND METHODS: The authors reviewed the records of all 18 patients with lacrimal gland adenoid cystic carcinoma surgically treated at their institution from 1997 to 2009 for imaging findings (blinded review) and histologic findings on evaluation of the lacrimal gland fossa. Preoperative CT and/or MRI findings were available for 17 patients. RESULTS: The 8 men and 10 women ranged in age from 9 to 69 years. American Joint Committee on Cancer tumor stages after preoperative imaging were as follows: T1N0M0, 2 patients; T2N0M0, 5 patients; T3aN0M0, 2 patients; T3bN0M0, 5 patients; T3bN0M1, 2 patients; T4bN0M0, one patient; and TxN0M0, one patient. Preoperative imaging suggested bony involvement of the lacrimal gland fossa in 13 patients (76.5%); this was histologically confirmed in 11 of the 13. Preoperative imaging suggested no bone involvement in 4 patients, 3 of whom had bone involvement by histology. Overall, 14 of 17 histologically evaluable cases (82.3%) had invasion of the lacrimal gland fossa. Histologic findings of bone/periosteal involvement led to upstaging of 3 tumors. Metastases developed in 8 of 18 patients and trended with basaloid histology (p = 0.066). CONCLUSIONS: Adenoid cystic carcinoma of the lacrimal gland is associated with bone invasion in essentially all but the smallest of tumors (T1). This high rate of bone involvement may warrant addressing the bony walls during surgery for adenoid cystic carcinoma of the lacrimal gland.

Prospective imaging assessment of mortality risk after head-and-neck radiotherapy.

PURPOSE: The optimal roles for imaging-based biomarkers in the management of head-and-neck cancer remain undefined. Unresolved questions include whether functional or anatomic imaging might improve mortality risk assessment for this disease. We addressed these issues in a prospective institutional trial. METHODS AND MATERIALS: Ninety-eight patients with locally advanced pharyngolaryngeal squamous cell cancer were enrolled. Each underwent pre- and post-chemoradiotherapy contrast-enhanced computed tomography (CT) and (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT imaging. Imaging parameters were correlated with survival outcomes. RESULTS: Low post-radiation primary tumor FDG avidity correlated with improved survival on multivariate analysis; so too did complete primary tumor response by CT alone. Although both imaging modalities lacked sensitivity, each had high specificity and negative predictive value for disease-specific mortality risk assessment. Kaplan-Meier estimates confirmed that both CT and FDG-PET/CT stratify patients into distinct high- and low-probability survivorship groups on the basis of primary tumor response to radiotherapy. Subset analyses demonstrated that the prognostic value for each imaging modality was primarily derived from patients at high risk for local treatment failure (human papillomavirus [HPV]-negative disease, nonoropharyngeal primary disease, or tobacco use). CONCLUSIONS: CT alone and FDG-PET/CT are potentially useful tools in head-and-neck cancer-specific mortality risk assessment after radiotherapy, particularly for selective use in cases of high-risk HPV-unrelated disease. Focus should be placed on corroboration and refinement of patient selection for imaging-based biomarkers in future studies.

Prospective risk-adjusted [18F]Fluorodeoxyglucose positron emission tomography and computed tomography assessment of radiation response in head and neck cancer.

PURPOSE: [(18)F]Fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomography (CT) imaging may improve assessment of radiation response in patients with head and neck cancer, but it is not yet known for which patients this is most useful. We conducted a prospective trial to identify patient populations likely to benefit from the addition of functional imaging to the assessment of radiotherapy response. PATIENTS AND METHODS: Ninety-eight patients with locally advanced cancer of the oropharynx, larynx, or hypopharynx were prospectively enrolled and treated with primary radiotherapy, with or without chemotherapy. Patients underwent FDG-PET/CT and contrast-enhanced CT imaging 8 weeks after completion of treatment. Functional and anatomic imaging response was correlated with clinical and pathologic response. Imaging accuracy was then compared between imaging modalities. RESULTS: Although postradiation maximum standard uptake values were significantly higher in nonresponders compared with responders, the positive and negative predictive values of FDG-PET/CT scanning were similar to those for CT alone in the unselected study population. Subset analyses revealed that FDG-PET/CT outperformed CT alone in response assessment for patients at high risk for treatment failure (those with human papillomavirus [HPV] -negative disease, nonoropharyngeal primaries, or history of tobacco use). No benefit to FDG-PET/CT was seen for low-risk patients lacking these features. CONCLUSION: These data do not support the broad application of FDG-PET/CT for radiation response assessment in unselected head and neck cancer patients. However, FDG-PET/CT may be the imaging modality of choice for patients with highest risk disease, particularly those with HPV-negative tumors. Optimal timing of FDG-PET/CT imaging after radiotherapy merits further investigation.

Fluorescence spectroscopy of oral tissue: Monte Carlo modeling with site-specific tissue properties.

A Monte Carlo model with site-specific input is used to predict depth-resolved fluorescence spectra from individual normal, inflammatory, and neoplastic oral sites. Our goal in developing this model is to provide a computational tool to study how the morphological characteristics of the tissue affect clinically measured spectra. Tissue samples from the measured sites are imaged using fluorescence confocal microscopy; autofluorescence patterns are measured as a function of depth and tissue sublayer for each individual site. These fluorescence distributions are used as input to the Monte Carlo model to generate predictions of fluorescence spectra, which are compared to clinically measured spectra on a site-by-site basis. A lower fluorescence intensity and longer peak emission wavelength observed in clinical spectra from dysplastic and cancerous sites are found to be associated with a decrease in measured fluorescence originating from the stroma or deeper fibrous regions, and an increase in the measured fraction of photons originating from the epithelium or superficial tissue layers. The simulation approach described here can be used to suggest an optical probe design that samples fluorescence at a depth that gives optimal separation in the spectral signal measured for benign, dysplastic, and cancerous oral mucosa.