The relative prognostic significance of nucleolar morphometry in invasive ductal breast cancer

Abstract

In a group of 65 patients with invasive ductal breast cancer with adequate follow-up for at least 5 years, the prognostic significance of nucleolar area morphometry was investigated. In general, non-survivors have larger and more pleomorphic nucleoli. A value of the standard deviation of the nucleolar area above 2.49 micron2 was almost exclusively found in non-survivors. This is the more interesting because several of these patients had a low mitotic activity index and small tumours, some of these having negative lymph nodes. Without nucleolar morphometry these patients would have been included in a favourable prognosis group. Although the sensitivity of nucleolar morphometry is low, the method can be used as an additional prognostic indicator. This is more important as nucleoli can in principle be automatically measured with digital image processing computers.

Cytopathological grading, as a predictor of histopathological grade, in ductal carcinoma (NOS) of breast, on air‐dried Diff‐Quik smears

“…The presence of nucleoli in histology has also been shown to be of prognostic significance. 15 Nucleoli are seen in cells actively engaged in growth and DNA synthesis and are seen in lactation and pregnancy, as well as conditions displaying highly anaplastic malignant cells. 42 The presence of nucleoli has been found useful in cytological grading both independently and in combination with the other cytological parameters.…”

“…A total score ranging from 6 (minimum) to 18 (maximum) was given to each case. The final tumor grade was assigned, by adding the different scores obtained, as follows: grade 1 (6 -10), grade 2 (11)(12)(13)(14), and grade 3 (15)(16)(17)(18).…”

“…Subsequently, a number of studies using FNAC concentrated on the nuclear parameters alone, including nuclear diameter, nuclear pleomorphism, and nucleoli, in order to predict histological grade, but with variable results in different series (40 -95% concordance rate). [11][12][13][14][15][16][17][18][19][20][21][22][23] Many significant cytological features, such as naked tumor nuclei, mitoses, necrosis, lymphoplasmacytic infiltrate, and invasion of stroma by the tumor cells, have not been thoroughly evaluated in the previous studies. Hence, there is a need for more studies to investigate and use all the available information on the smear, in order to establish valid criteria that can be applied to FNAC material to predict histological grade.…”

Objective malignancy grading: A review emphasizing unbiased stereology applied to breast tumors

“…For instance, interobserver studies of 2D and 3D mean nuclear size estimates in breast cancer (122,139) as well as in some other malignant tumors (28,96,123), generally show coefficients of corre-lation in the vicinity of 0.9 and slopes of regression lines not significantly different from unity. Others have found a high interobserver reproducibility of mean nucleolar profile size estimates (139,140) and ofvolume densities of epithelium and stromal collagen as well (141). It is noticeable that the reported high reproducibility of quantitative nuclear parameters is in stark contrast to the significant observer variation of morphologic, qualitative nuclear grading (23,25,134).…”

“…Similarly, in a previosly described series including more than 200 breast cancer patients with long follow-up (159), estimates of Vv (nuc) could replace mitotic counts in the so-called "Multivariate Prognostic Index" (MpI) without loss of prognostic accuracy (Ladekarl M, Baak JPA, Voorhorst FJ, Snrrensen FB, Matze-Cok E (submitted)), the original MPI being based on a combination of lymph node status, tumor diameter and a mitotic count (61). For instance, in studies of breast cancer the prognostic value of estimates of the mean nucleadcytoplasmatic ratio and of volume densities of stroma, epithelium and necrosis has been found not to be independent of that of variables of nuclear size and mitoses, and a similar disappointing result has been achieved with estimates of mean nucleolar profile size (61,140,171). With respect to most stereologic variables, including those obtained by the Cavalieri technique and the optic disector, a need for testing in follow-up studies remains.…”